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1.
Carolina Riveros Agnes Dechartres Elodie Perrodeau Romana Haneef Isabelle Boutron Philippe Ravaud 《PLoS medicine》2013,10(12)
Background
The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals.Methods and Findings
We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose).From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001).The main study limitation was that we considered only the publication describing the results for the primary outcomes.Conclusions
Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article. Please see later in the article for the Editors'' Summary 相似文献2.
Background
Result publication is the key step to improve the transparency of clinical trials.Objective
To investigate the result publication rate of Chinese trials registered in World Health Organization (WHO) primary registries.Method
We searched 11 WHO primary registries for Chinese trials records. The progress of each trial was analyzed. We searched for the full texts of result publications cited in the registration records. For completed trials without citations, we searched PubMed, Embase, Chinese Biomedical Literature Database (Chinese), China Knowledge Resource Integrated Database, and Chinese Science and Technology Periodicals Database for result publications. The search was conducted on July 14, 2009. We also called the investigators of completed trials to ask about results publication.Results
We identified 1294 Chinese trials records (428 in ChiCTR,743 in clinicaltrials.gov,55 in ISRCTN, 21 in ACTRN). A total of 443 trials had been completed. The publication rate of the Chinese trials in WHO primary registries is 35.2%(156/443).The publication rate of Chinese trials in clinicaltrials.gov, ChiCTR, ISRCTN, and ACRTN was 36.5% (53/145), 36.3% (89/245), 26.0%(9/44), and 55.6%(5/9), respectively. The publication rate of trials sponsored by industry(23.8%) was lower than that of sponsored by central and local government(31.7%), hospital(35.1%), and universities (40.7%). The publication rate for randomized trials was higher than that of cohort study and case-control study (33.2% versus 16.7%, 22.2%). The publication rate for interventional studies and observational studies was similar(33.4% versus 33.3%).Conclusion
The publication rate of the registered Chinese trials was low, with no significant difference between ChiCTR and clinicaltrials.gov. An effective mechanism is needed to promote publication of results for registered trials in China. 相似文献3.
Objective
We assessed the adequacy of randomized controlled trial (RCT) registration, changes to registration data and reporting completeness for articles in ICMJE journals during 2.5 years after registration requirement policy.Methods
For a set of 149 reports of 152 RCTs with ClinicalTrials.gov registration number, published from September 2005 to April 2008, we evaluated the completeness of 9 items from WHO 20-item Minimum Data Set relevant for assessing trial quality. We also assessed changes to the registration elements at the Archive site of ClinicalTrials.gov and compared published and registry data.Results
RCTs were mostly registered before 13 September 2005 deadline (n = 101, 66.4%); 118 (77.6%) started recruitment before and 31 (20.4%) after registration. At the time of registration, 152 RCTs had a total of 224 missing registry fields, most commonly ‘Key secondary outcomes’ (44.1% RCTs) and ‘Primary outcome’ (38.8%). More RCTs with post-registration recruitment had missing Minimum Data Set items than RCTs with pre-registration recruitment: 57/118 (48.3%) vs. 24/31 (77.4%) (χ2 1 = 7.255, P = 0.007). Major changes in the data entries were found for 31 (25.2%) RCTs. The number of RCTs with differences between registered and published data ranged from 21 (13.8%) for Study type to 118 (77.6%) for Target sample size.Conclusions
ICMJE journals published RCTs with proper registration but the registration data were often not adequate, underwent substantial changes in the registry over time and differed in registered and published data. Editors need to establish quality control procedures in the journals so that they continue to contribute to the increased transparency of clinical trials. 相似文献4.
Introduction
Although selective reporting of clinical trial results introduces bias into evidence based clinical decision making, publication bias in pediatric epilepsy is unknown today. Since there is a considerable ambiguity in the treatment of an important and common clinical problem, pediatric seizures, we assessed the public availability of results of phase 3 clinical trials that evaluated treatments of seizures in children and adolescents as a surrogate for the extent of publication bias in pediatric epilepsy.Methods
We determined the proportion of published and unpublished study results of phase 3 clinical trials that were registered as completed on ClinicalTrials.gov. We searched ClinicalTrials.gov, PubMed, and Google Scholar for publications and contacted principal investigators or sponsors. The analysis was performed according to STROBE criteria.Results
Considering studies that were completed before 2014 (N = 99), 75 (76%) pediatric phase 3 clinical trials were published but 24 (24%) remained unpublished. The unpublished studies concealed evidence from 4,437 patients. Mean time-to-publication was 25 SD ± 15.6 months, more than twice as long as mandated.Conclusion
Ten years after the ICMJE’s clinical trials registration initiative there is still a considerable amount of selective reporting and delay of publication that potentially distorts the body of evidence in the treatment of pediatric seizures. 相似文献5.
Sekeres M Gold JL Chan AW Lexchin J Moher D Van Laethem ML Maskalyk J Ferris L Taback N Rochon PA 《PloS one》2008,3(2):e1610
Background
In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. The objective is to examine the proportion of registered clinical trials providing valid scientific leadership information.Methodology/Principal Findings
We reviewed clinical trial entries listing Canadian investigators in the two largest international and public trial registers, the International Standard Randomized Controlled Trial Number (ISRCTN) register, and ClinicalTrials.gov. The main outcome measures were the proportion of clinical trials reporting valid contact information for the trials'' Principal Investigator (PI)/Co-ordinating Investigator/Study Chair/Site PI, and trial e-mail contact address, stratified by funding source, recruiting status, and register. A total of 1388 entries (142 from ISRCTN and 1246 from ClinicalTrials.gov) comprised our sample. We found non-compliance with mandatory registration requirements regarding scientific leadership and trial contact information. Non-industry and partial industry funded trials were significantly more likely to identify the individual responsible for scientific leadership (OR = 259, 95% CI: 95–701) and to provide a contact e-mail address (OR = 9.6, 95% CI: 6.6–14) than were solely industry funded trials.Conclusions/Significance
Despite the requirements set by WHO and ICMJE, data on scientific leadership and contact e-mail addresses are frequently omitted from clinical trials registered in the two leading public clinical trial registers. To promote accountability and transparency in clinical trials research, public clinical trials registers should ensure adequate monitoring of trial registration to ensure completion of mandatory contact information fields identifying scientific leadership 相似文献6.
Shahin Lockman Michael Hughes Fred Sawe Yu Zheng James McIntyre Tsungai Chipato Aida Asmelash Mohammed Rassool Sylvester Kimaiyo Douglas Shaffer Mina Hosseinipour Lerato Mohapi Francis Ssali Margret Chibowa Farida Amod Elias Halvas Evelyn Hogg Beverly Alston-Smith Laura Smith Robert Schooley John Mellors Judith Currier the OCTANE ACTG A/OCTANE Study Team 《PLoS medicine》2012,9(6)
Background
Nevirapine (NVP) is widely used in antiretroviral treatment (ART) of HIV-1 globally. The primary objective of the AA5208/OCTANE trial was to compare the efficacy of NVP-based versus lopinavir/ritonavir (LPV/r)-based initial ART.Methods and Findings
In seven African countries (Botswana, Kenya, Malawi, South Africa, Uganda, Zambia, and Zimbabwe), 500 antiretroviral-naïve HIV-infected women with CD4<200 cells/mm3 were enrolled into a two-arm randomized trial to initiate open-label ART with tenofovir (TDF)/emtricitabine (FTC) once/day plus either NVP (n = 249) or LPV/r (n = 251) twice/day, and followed for ≥48 weeks. The primary endpoint was time from randomization to death or confirmed virologic failure ([VF]) (plasma HIV RNA<1 log10 below baseline 12 weeks after treatment initiation, or ≥400 copies/ml at or after 24 weeks), with comparison between treatments based on hazard ratios (HRs) in intention-to-treat analysis. Equivalence of randomized treatments was defined as finding the 95% CI for HR for virological failure or death in the range 0.5 to 2.0. Baseline characteristics were (median): age = 34 years, CD4 = 121 cells/mm3, HIV RNA = 5.2 log10copies/ml. Median follow-up = 118 weeks; 29 (6%) women were lost to follow-up. 42 women (37 VFs, five deaths; 17%) in the NVP and 50 (43 VFs, seven deaths; 20%) in the LPV/r arm reached the primary endpoint (HR 0.85, 95% CI 0.56–1.29). During initial assigned treatment, 14% and 16% of women receiving NVP and LPV/r experienced grade 3/4 signs/symptoms and 26% and 22% experienced grade 3/4 laboratory abnormalities. However, 35 (14%) women discontinued NVP because of adverse events, most in the first 8 weeks, versus none for LPV/r (p<0.001). VF, death, or permanent treatment discontinuation occurred in 80 (32%) of NVP and 54 (22%) of LPV/r arms (HR = 1.7, 95% CI 1.2–2.4), with the difference primarily due to more treatment discontinuation in the NVP arm. 13 (45%) of 29 women tested in the NVP versus six (15%) of 40 in the LPV/r arm had any drug resistance mutation at time of VF.Conclusions
Initial ART with NVP+TDF/FTC demonstrated equivalent virologic efficacy but higher rates of treatment discontinuation and new drug resistance compared with LPV/r+TDF/FTC in antiretroviral-naïve women with CD4<200 cells/mm3.Trial registration
ClinicalTrials.gov NCT00089505 Please see later in the article for the Editors'' Summary 相似文献7.
Ronald H. Gray David Serwadda Aaron A. R. Tobian Michael Z. Chen Frederick Makumbi Tara Suntoke Godfrey Kigozi Fred Nalugoda Boaz Iga Thomas C. Quinn Lawrence H. Moulton Oliver Laeyendecker Steven J. Reynolds Xiangrong Kong Maria J. Wawer 《PLoS medicine》2009,6(11)
Background
Randomized trials show that male circumcision (MC) reduces the incidence of HIV and herpes simplex virus type 2 (HSV-2) infections, and symptomatic genital ulcer disease (GUD). We assessed the role of GUD and HSV-2 in the protection against HIV afforded by MC.Methods and Findings
HIV-uninfected men were randomized to immediate (n = 2,756) or delayed MC (n = 2,775) in two randomized trials in Rakai, Uganda. GUD symptoms, HSV-2 status, and HIV acquisition were determined at enrollment and at 6, 12, and 24 mo of follow up. Ulcer etiology was assessed by PCR. We estimated the prevalence and prevalence risk ratios (PRRs) of GUD in circumcised versus uncircumcised men and assessed the effects of HSV-2 serostatus as a risk-modifying factor for GUD. We estimated the proportion of the effect of MC on HIV acquisition that was mediated by symptomatic GUD, and by HSV-2 infection. Circumcision significantly reduced symptomatic GUD in HSV-2-seronegative men (PRR = 0.51, 95% [confidence interval] CI 0.43–0.74), HSV-2-seropositive men (PRR = 0.66, 95% CI 0.51–0.69), and in HSV-2 seroconverters (PRR = 0.48, 95% CI 0.30–0.79). The proportion of acute ulcers due to HSV-2 detected by PCR was 48.0% in circumcised men and 39.3% in uncircumcised men (χ2 p = 0.62). Circumcision reduced the risk of HIV acquisition in HSV-2 seronegative men (incidence rate ratio [IRR] = 0.34, 95% CI 0.15–0.81), and potentially in HSV-2 seroconverters (IRR = 0.56, 95% CI 0.19–1.57; not significant), but not in men with prevalent HSV-2 at enrollment (IRR = 0.89, 95% CI 0.49–1.60). The proportion of reduced HIV acquisition in circumcised men mediated by reductions in symptomatic GUD was 11.2% (95% CI 5.0–38.0), and the proportion mediated by reduced HSV-2 incidence was 8.6% (95% CI −1.2 to 77.1).Conclusions
Circumcision reduced GUD irrespective of HSV-2 status, but this reduction played only a modest role in the protective effect of circumcision on HIV acquisition.NIH Trial registration
ClinicalTrials.gov NCT00425984Gates Foundation Trial registration
ClinicalTrials.gov NCT00124878 Please see later in the article for the Editors'' Summary 相似文献8.
Andrew R. Zolopa Janet Andersen Lauren Komarow Ian Sanne Alejandro Sanchez Evelyn Hogg Carol Suckow William Powderly for the ACTG A study team 《PloS one》2009,4(5)
Background
Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined.Methods and Findings
A5164 was a randomized strategy trial of “early ART” - given within 14 days of starting acute OI treatment versus “deferred ART” - given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) ≥50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS.282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively.The difference in the primary endpoint did not reach statistical significance: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27–0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30–0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events.Conclusions
Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications.Trial Registration
ClinicalTrials.gov NCT00055120 相似文献9.
Nicolas Senn Patricia Rarau Danielle I. Stanisic Leanne Robinson Céline Barnadas Doris Manong Mary Salib Jonah Iga Nandao Tarongka Serej Ley Anna Rosanas-Urgell John J. Aponte Peter A. Zimmerman James G. Beeson Louis Schofield Peter Siba Stephen J. Rogerson John C. Reeder Ivo Mueller 《PLoS medicine》2012,9(3)
Background
Intermittent preventive treatment in infants (IPTi) has been shown in randomized trials to reduce malaria-related morbidity in African infants living in areas of high Plasmodium falciparum (Pf) transmission. It remains unclear whether IPTi is an appropriate prevention strategy in non-African settings or those co-endemic for P. vivax (Pv).Methods and Findings
In this study, 1,121 Papua New Guinean infants were enrolled into a three-arm placebo-controlled randomized trial and assigned to sulfadoxine-pyrimethamine (SP) (25 mg/kg and 1.25 mg/kg) plus amodiaquine (AQ) (10 mg/kg, 3 d, n = 374), SP plus artesunate (AS) (4 mg/kg, 3 d, n = 374), or placebo (n = 373), given at 3, 6, 9 and 12 mo. Both participants and study teams were blinded to treatment allocation. The primary end point was protective efficacy (PE) against all episodes of clinical malaria from 3 to 15 mo of age. Analysis was by modified intention to treat. The PE (compared to placebo) against clinical malaria episodes (caused by all species) was 29% (95% CI, 10–43, p≤0.001) in children receiving SP-AQ and 12% (95% CI, −11 to 30, p = 0.12) in those receiving SP-AS. Efficacy was higher against Pf than Pv. In the SP-AQ group, Pf incidence was 35% (95% CI, 9–54, p = 0.012) and Pv incidence was 23% (95% CI, 0–41, p = 0.048) lower than in the placebo group. IPTi with SP-AS protected only against Pf episodes (PE = 31%, 95% CI, 4–51, p = 0.027), not against Pv episodes (PE = 6%, 95% CI, −24 to 26, p = 0.759). Number of observed adverse events/serious adverse events did not differ between treatment arms (p>0.55). None of the serious adverse events were thought to be treatment-related, and the vomiting rate was low in both treatment groups (1.4%–2.0%). No rebound in malaria morbidity was observed for 6 mo following the intervention.Conclusions
IPTi using a long half-life drug combination is efficacious for the prevention of malaria and anemia in infants living in a region highly endemic for both Pf and Pv.Trial registration
ClinicalTrials.gov NCT00285662 Please see later in the article for the Editors'' Summary 相似文献10.
Neela D. Goswami Christopher D. Pfeiffer John R. Horton Karen Chiswell Asba Tasneem Ephraim L. Tsalik 《PloS one》2013,8(10)
Background
There is a paucity of clinical trials informing specific questions faced by infectious diseases (ID) specialists. The ClinicalTrials.gov registry offers an opportunity to evaluate the ID clinical trials portfolio.Methods
We examined 40,970 interventional trials registered with ClinicalTrials.gov from 2007–2010, focusing on study conditions and interventions to identify ID-related trials. Relevance to ID was manually confirmed for each programmatically identified trial, yielding 3570 ID trials and 37,400 non-ID trials for analysis.Results
The number of ID trials was similar to the number of trials identified as belonging to cardiovascular medicine (n = 3437) or mental health (n = 3695) specialties. Slightly over half of ID trials were treatment-oriented trials (53%, vs. 77% for non-ID trials) followed by prevention (38%, vs. 8% in non-ID trials). ID trials tended to be larger than those of other specialties, with a median enrollment of 125 subjects (interquartile range [IQR], 45–400) vs. 60 (IQR, 30–160) for non-ID trials. Most ID studies are randomized (73%) but nonblinded (56%). Industry was the funding source in 51% of ID trials vs. 10% that were primarily NIH-funded. HIV-AIDS trials constitute the largest subset of ID trials (n = 815 [23%]), followed by influenza vaccine (n = 375 [11%]), and hepatitis C (n = 339 [9%]) trials. Relative to U.S. and global mortality rates, HIV-AIDS and hepatitis C virus trials are over-represented, whereas lower respiratory tract infection trials are under-represented in this large sample of ID clinical trials.Conclusions
This work is the first to characterize ID clinical trials registered in ClinicalTrials.gov, providing a framework to discuss prioritization, methodology, and policy. 相似文献11.
12.
Kenneth D. Coburn Sherry Marcantonio Robert Lazansky Maryellen Keller Nancy Davis 《PLoS medicine》2012,9(7)
Background
Improving the health of chronically ill older adults is a major challenge facing modern health care systems. A community-based nursing intervention developed by Health Quality Partners (HQP) was one of 15 different models of care coordination tested in randomized controlled trials within the Medicare Coordinated Care Demonstration (MCCD), a national US study. Evaluation of the HQP program began in 2002. The study reported here was designed to evaluate the survival impact of the HQP program versus usual care up to five years post-enrollment.Methods and Findings
HQP enrolled 1,736 adults aged 65 and over, with one or more eligible chronic conditions (coronary artery disease, heart failure, diabetes, asthma, hypertension, or hyperlipidemia) during the first six years of the study. The intervention group (n = 873) was offered a comprehensive, integrated, and tightly managed system of care coordination, disease management, and preventive services provided by community-based nurse care managers working collaboratively with primary care providers. The control group (n = 863) received usual care. Overall, a 25% lower relative risk of death (hazard ratio [HR] 0.75 [95% CI 0.57–1.00], p = 0.047) was observed among intervention participants with 86 (9.9%) deaths in the intervention group and 111 (12.9%) deaths in the control group during a mean follow-up of 4.2 years. When covariates for sex, age group, primary diagnosis, perceived health, number of medications taken, hospital stays in the past 6 months, and tobacco use were included, the adjusted HR was 0.73 (95% CI 0.55–0.98, p = 0.033). Subgroup analyses did not demonstrate statistically significant interaction effects for any subgroup. No suspected program-related adverse events were identified.Conclusions
The HQP model of community-based nurse care management appeared to reduce all-cause mortality in chronically ill older adults. Limitations of the study are that few low-income and non-white individuals were enrolled and implementation was in a single geographic region of the US. Additional research to confirm these findings and determine the model''s scalability and generalizability is warranted.Trial Registration
ClinicalTrials.gov NCT01071967 Please see later in the article for the Editors'' Summary 相似文献13.
Objective
In an effort to understand how results of human clinical trials are made public, we analyze a large set of clinical trials registered at ClinicalTrials.gov, the world’s largest clinical trial registry.Materials and Methods
We considered two trial result artifacts: (1) existence of a trial result journal article that is formally linked to a registered trial or (2) the deposition of a trial’s basic summary results within the registry.Results
The study sample consisted of 8907 completed, interventional, phase 2-or-higher clinical trials that were completed in 2006-2009. The majority of trials (72.2%) had no structured trial-article link present. A total of 2367 trials (26.6%) deposited basic summary results within the registry. Of those , 969 trials (10.9%) were classified as trials with extended results and 1398 trials (15.7%) were classified as trials with only required basic results. The majority of the trials (54.8%) had no evidence of results, based on either linked result articles or basic summary results (silent trials), while a minimal number (9.2%) report results through both registry deposition and publication.Discussion
Our study analyzes the body of linked knowledge around clinical trials (which we refer to as the “trialome”). Our results show that most trials do not report results and, for those that do, there is minimal overlap in the types of reporting. We identify several mechanisms by which the linkages between trials and their published results can be increased.Conclusion
Our study shows that even when combining publications and registry results, and despite availability of several information channels, trial sponsors do not sufficiently meet the mandate to inform the public either via a linked result publication or basic results submission. 相似文献14.
Sunil Sazawal Usha Dhingra Girish Hiremath Archana Sarkar Pratibha Dhingra Arup Dutta Priti Verma Venugopal P. Menon Robert E. Black 《PloS one》2010,5(8)
Background
Recent reviews suggest common infectious diseases continue to be a major cause of death among preschool children in developing countries. Identification of feasible strategies to combat this disease burden is an important public health need. We evaluated the efficacy of adding prebiotic oligosaccharide and probiotic Bifidobacterium lactis HN019 to milk, in preventing diarrhea, respiratory infections and severe illnesses, in children aged 1–4 years as part of a four group study design, running two studies simultaneously.Methods and Findings
In a community based double-masked, randomized controlled trial, children 1–3 years of age, willing to participate, were randomly allocated to receive either control milk (Co; n = 312) or the same milk fortified with 2.4 g/day of prebiotic oligosaccharide and 1.9×107 colony forming unit (c.f.u)/day of probiotic Bifidobacterium lactis HN019 (PP; n = 312). Children were followed up for 1 year providing data for 1–4 years. Biweekly household surveillance was conducted to gather information on compliance and morbidity. Both study groups were comparable at baseline; compliance to intervention was similar. Overall, there was no effect of prebiotic and probiotic on diarrhea (6% reduction, 95% Confidence Interval [CI]: −1 to 12%; p = 0.08). Incidence of dysentery episodes was reduced by 21% (95% CI: 0 to 38%; p = 0.05). Incidence of pneumonia was reduced by 24% (95% CI: 0 to 42%; p = 0.05) and severe acute lower respiratory infection (ALRI) by 35% (95% CI: 0 to 58%; p = 0.05). Compared to children in Co group, children in PP group had 16% (95% CI: 5 to 26%, p = 0.004) and 5% (95% CI: 0 to 10%; p = 0.05) reduction in days with severe illness and high fever respectively.Conclusions/Significance
Milk can be a good medium for delivery of prebiotic and probiotic and resulted in significant reduction of dysentery, respiratory morbidity and febrile illness. Overall, impact of diarrhea was not significant. These findings need confirmation in other settings.Trial Registration
ClinicalTrials.gov NCT00255385 相似文献15.
Afif Ben Salah Pierre A. Buffet Gloria Morizot Nathalie Ben Massoud Amor Zaatour Nissaf Ben Alaya Nabil Bel Haj Hamida Zaher El Ahmadi Matthew T. Downs Philip L. Smith Koussay Dellagi Max Gr?gl 《PLoS neglected tropical diseases》2009,3(5)
Background
Cutaneous leishmaniasis (CL) is a disfiguring disease that confronts clinicians with a quandary: leave patients untreated or engage in a complex or toxic treatment. Topical treatment of CL offers a practical and safe option. Accordingly, the treatment of CL with WR279,396, a formulation of paromomycin and gentamicin in a hydrophilic base, was investigated in a phase 2 clinical study in Tunisia and France.Methods
A phase 2, randomized, double blind, vehicle-controlled study was conducted to assess the safety and efficacy of topical WR279,396 when applied twice a day for 20 days as treatment for parasitologically confirmed CL. The study protocol established the primary efficacy end point as complete clinical response (CCR) defined as 50% or greater reduction in the ulceration size of an index lesion by day 50 (D50) followed by complete re-epithelialization by D100, and no relapse through D180.Results
Ninety-two subjects were randomized. Leishmania major was identified in 66 of 68 isolates typed (97%). In the intent-to-treat population, 47 of 50 WR279,396 treated participants (94%) met the definition of CCR, compared with 30 of 42 vehicle-placebo participants (71%) [p = 0.0045]. Erythema occurred in 30% and 24% of participants receiving WR279,396 and placebo, respectively [p = 0.64]. There was no clinical or laboratory evidence of systemic toxicity.Conclusion
Application of WR279,396 for 20 days was found to be safe and effective in treating L. major CL, and offers great potential as a new, simple, easily applicable, and inexpensive topical therapy for this neglected disease.Trial Registration
ClinicalTrials.gov NCT00703924 相似文献16.
Clara Menéndez Azucena Bardají Betuel Sigauque Sergi Sanz John J. Aponte Samuel Mabunda Pedro L. Alonso 《PloS one》2010,5(2)
Background
In the global context of a reduction of under-five mortality, neonatal mortality is an increasingly relevant component of this mortality. Malaria in pregnancy may affect neonatal survival, though no strong evidence exists to support this association.Methods
In the context of a randomised, placebo-controlled trial of intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine (SP) in 1030 Mozambican pregnant women, 997 newborns were followed up until 12 months of age. There were 500 live borns to women who received placebo and 497 to those who received SP.Findings
There were 58 infant deaths; 60.4% occurred in children born to women who received placebo and 39.6% to women who received IPTp (p = 0.136). There were 25 neonatal deaths; 72% occurred in the placebo group and 28% in the IPTp group (p = 0.041). Of the 20 deaths that occurred in the first week of life, 75% were babies born to women in the placebo group and 25% to those in the IPTp group (p = 0.039). IPTp reduced neonatal mortality by 61.3% (95% CI 7.4%, 83.8%); p = 0.024].Conclusions
Malaria prevention with SP in pregnancy can reduce neonatal mortality. Mechanisms associated with increased malaria infection at the end of pregnancy may explain the excess mortality in the malaria less protected group. Alternatively, SP may have reduced the risk of neonatal infections. These findings are of relevance to promote the implementation of IPTp with SP, and provide insights into the understanding of the pathophysiological mechanisms through which maternal malaria affects fetal and neonatal health.Trial Registration
ClinicalTrials.gov NCT00209781 相似文献17.
Mahamadou S. Sissoko Abdoulaye Dabo Hamidou Traoré Mouctar Diallo Boubacar Traoré Drissa Konaté Boubacar Niaré Moussa Diakité Bourama Kamaté Abdrahamane Traoré Aboudramane Bathily Amadou Tapily Ousmane B. Touré Sarah Cauwenbergh Herwig F. Jansen Ogobara K. Doumbo 《PloS one》2009,4(10)
Background
This study was conducted to determine the efficacy of the antimalarial artemisinin-based combination therapy (ACT) artesunate +sulfamethoxypyrazine/pyrimethamine (As+SMP), administered in doses used for malaria, to treat Schistosoma haematobium in school aged children.Methodology/Principal Findings
The study was conducted in Djalakorodji, a peri-urban area of Bamako, Mali, using a double blind setup in which As+SMP was compared with praziquantel (PZQ). Urine samples were examined for Schistosoma haematobium on days −1, 0, 28 and 29. Detection of haematuria, and haematological and biochemical exams were conducted on day 0 and day 28. Clinical exams were performed on days 0, 1, 2, and 28. A total of 800 children were included in the trial. The cure rate obtained without viability testing was 43.9% in the As+SMP group versus 53% in the PZQ group (Chi2 = 6.44, p = 0.011). Egg reduction rates were 95.6% with PZQ in comparison with 92.8% with As+SMP, p = 0.096. The proportion of participants who experienced adverse events related to the medication was 0.5% (2/400) in As+SMP treated children compared to 2.3% (9/399) in the PZQ group (p = 0.033). Abdominal pain and vomiting were the most frequent adverse events in both treatment arms. All adverse events were categorized as mild.Conclusions/Significance
The study demonstrates that PZQ was more effective than As+SMP for treating Schistosoma haematobium. However, the safety and tolerability profile of As+SMP was similar to that seen with PZQ. Our findings suggest that further investigations seem justifiable to determine the dose/efficacy/safety pattern of As+SMP in the treatment of Schistosoma infections.Trial Registration
ClinicalTrials.gov NCT00510159 http://clinicaltrials.gov/ct2/show/NCT00510159 相似文献18.
Background
One of the main strategies to control tuberculosis (TB) is to find and treat people with active disease. Unfortunately, the case detection rates remain low in many countries. Thus, we need interventions to find and treat sufficient number of patients to control TB. We investigated whether involving health extension workers (HEWs: trained community health workers) in TB control improved smear-positive case detection and treatment success rates in southern Ethiopia.Methodology/Principal Finding
We carried out a community-randomized trial in southern Ethiopia from September 2006 to April 2008. Fifty-one kebeles (with a total population of 296, 811) were randomly allocated to intervention and control groups. We trained HEWs in the intervention kebeles on how to identify suspects, collect sputum, and provide directly observed treatment. The HEWs in the intervention kebeles advised people with productive cough of 2 weeks or more duration to attend the health posts. Two hundred and thirty smear-positive patients were identified from the intervention and 88 patients from the control kebeles. The mean case detection rate was higher in the intervention than in the control kebeles (122.2% vs 69.4%, p<0.001). In addition, more females patients were identified in the intervention kebeles (149.0 vs 91.6, p<0.001). The mean treatment success rate was higher in the intervention than in the control kebeles (89.3% vs 83.1%, p = 0.012) and more for females patients (89.8% vs 81.3%, p = 0.05).Conclusions/Significance
The involvement of HEWs in sputum collection and treatment improved smear-positive case detection and treatment success rate, possibly because of an improved service access. This could be applied in settings with low health service coverage and a shortage of health workers.Trial Registration
ClinicalTrials.gov NCT00803322 相似文献19.
Background
Previous studies of drug trials submitted to regulatory authorities have documented selective reporting of both entire trials and favorable results. The objective of this study is to determine the publication rate of efficacy trials submitted to the Food and Drug Administration (FDA) in approved New Drug Applications (NDAs) and to compare the trial characteristics as reported by the FDA with those reported in publications.Methods and Findings
This is an observational study of all efficacy trials found in approved NDAs for New Molecular Entities (NMEs) from 2001 to 2002 inclusive and all published clinical trials corresponding to the trials within the NDAs. For each trial included in the NDA, we assessed its publication status, primary outcome(s) reported and their statistical significance, and conclusions. Seventy-eight percent (128/164) of efficacy trials contained in FDA reviews of NDAs were published. In a multivariate model, trials with favorable primary outcomes (OR = 4.7, 95% confidence interval [CI] 1.33–17.1, p = 0.018) and active controls (OR = 3.4, 95% CI 1.02–11.2, p = 0.047) were more likely to be published. Forty-one primary outcomes from the NDAs were omitted from the papers. Papers included 155 outcomes that were in the NDAs, 15 additional outcomes that favored the test drug, and two other neutral or unknown additional outcomes. Excluding outcomes with unknown significance, there were 43 outcomes in the NDAs that did not favor the NDA drug. Of these, 20 (47%) were not included in the papers. The statistical significance of five of the remaining 23 outcomes (22%) changed between the NDA and the paper, with four changing to favor the test drug in the paper (p = 0.38). Excluding unknowns, 99 conclusions were provided in both NDAs and papers, nine conclusions (9%) changed from the FDA review of the NDA to the paper, and all nine did so to favor the test drug (100%, 95% CI 72%–100%, p = 0.0039).Conclusions
Many trials were still not published 5 y after FDA approval. Discrepancies between the trial information reviewed by the FDA and information found in published trials tended to lead to more favorable presentations of the NDA drugs in the publications. Thus, the information that is readily available in the scientific literature to health care professionals is incomplete and potentially biased. 相似文献20.
David J. Bacon Doug Tang Carola Salas Norma Roncal Carmen Lucas Lucia Gerena Lorena Tapia A. Alejandro Llanos-Cuentas Coralith Garcia Lelv Solari Dennis Kyle Alan J. Magill 《PloS one》2009,4(8)