An open label,block randomized,community study of the safety and efficacy of co-administered ivermectin,diethylcarbamazine plus albendazole vs. diethylcarbamazine plus albendazole for lymphatic filariasis in India

BackgroundBetter drug regimens for mass drug administration (MDA) could accelerate the Global Programme to Eliminate Lymphatic Filariasis (LF). This community study was designed to compare the safety and efficacy of MDA with IDA (ivermectin, diethylcarbamazine and albendazole) or DA (diethylcarbamazine and albendazole) in India.Methodology/Principal findingsThis two-armed, open-labelled, block randomised, community study was conducted in LF endemic villages in Yadgir district, Karnataka, India. Consenting participants ≥5 years of age were tested for circulating filarial antigenemia (CFA) and microfilaremia (Mf) before treatment with a single oral dose of IDA or DA. Adverse events (AEs) were monitored actively for two days and passively for five more days. Persons with positive CFA or Mf tests at baseline were retested 12-months post-treatment to assess treatment efficacy.Baseline CFA and Mf-rates were 26.4% and 6.9% in IDA and 24.5% and 6.4% in DA villages respectively. 4758 and 4160 participants received IDA and DA. Most AEs were mild after both treatments; fewer than 0.1% of participants experienced AEs with severity > grade 1. No serious AEs were observed. Fever, headache and dizziness were the most common AEs. AE rates were slightly higher after IDA than DA (8.3% vs. 6.4%, P<0.01). AEs were more frequent in females and Mf-positives after either treatment, but significantly more frequent after IDA (40.5% vs 20.2%, P < 0.001).IDA was more effective for clearing Mf than DA (84% vs. 61.8%, P < 0.001). Geometric mean Mf counts per 60μl in retested Mf-positives decreased by 96.4% from 11.8 after IDA and by 90.0% from 9.5 after DA. Neither treatment was effective for clearing CFA.Conclusions/SignificanceIDA had an acceptable safety profile and was more effective for clearing Mf than DA. With adequate compliance and medical support to manage AEs, IDA has the potential to accelerate LF elimination in India.Trial registrationClinical Trial Registry of India (CTRI No/2016/10/007399)     

Safety and efficacy of mass drug administration with a single-dose triple-drug regimen of albendazole + diethylcarbamazine + ivermectin for lymphatic filariasis in Papua New Guinea: An open-label,cluster-randomised trial

BackgroundPapua New Guinea (PNG) has a high burden of lymphatic filariasis (LF) caused by Wuchereria bancrofti, with an estimated 4.2 million people at risk of infection. A single co-administered dose of ivermectin, diethylcarbamazine and albendazole (IDA) has been shown to have superior efficacy in sustained clearance of microfilariae compared to diethylcarbamazine and albendazole (DA) in small clinical trials. A community-based cluster-randomised trial of DA versus IDA was conducted to compare the safety and efficacy of IDA and DA for LF in a moderately endemic, treatment-naive area in PNG.MethodologyAll consenting, eligible residents of 24 villages in Bogia district, Madang Province, PNG were enrolled, screened for W. bancrofti antigenemia and microfilaria (Mf) and randomised to receive IDA (N = 2382) or DA (N = 2181) according to their village of residence. Adverse events (AE) were assessed by active follow-up for 2 days and passive follow-up for an additional 5 days. Antigen-positive participants were re-tested one year after MDA to assess treatment efficacy.Principal findingsOf the 4,563 participants enrolled, 96% were assessed for AEs within 2 days after treatment. The overall frequency of AEs were similar after either DA (18%) or IDA (20%) treatment. For those individuals with AEs, 87% were mild (Grade 1), 13% were moderate (Grade 2) and there were no Grade 3, Grade 4, or serious AEs (SAEs). The frequency of AEs was greater in Mf-positive than Mf-negative individuals receiving IDA (39% vs 20% p<0.001) and in Mf-positive participants treated with IDA (39%), compared to those treated with DA (24%, p = 0.023). One year after treatment, 64% (645/1013) of participants who were antigen-positive at baseline were re-screened and 74% of these participants (475/645) remained antigen positive. Clearance of Mf was achieved in 96% (52/54) of infected individuals in the IDA arm versus 84% (56/67) of infected individuals in the DA arm (relative risk (RR) 1.15; 95% CI, 1.02 to 1.30; p = 0.019). Participants receiving DA treatment had a 4-fold higher likelihood of failing to clear Mf (RR 4.67 (95% CI: 1.05 to 20.67; p = 0.043). In the DA arm, a significant predictor of failure to clear was baseline Mf density (RR 1.54; 95% CI, 1.09 to 2.88; p = 0.007).ConclusionIDA was well tolerated and more effective than DA for clearing Mf. Widespread use of this regimen could accelerate LF elimination in PNG.Trial registrationRegistration number {"type":"clinical-trial","attrs":{"text":"NCT02899936","term_id":"NCT02899936"}}NCT02899936; https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02899936","term_id":"NCT02899936"}}NCT02899936.     

Treatment of co-infection with bancroftian filariasis and onchocerciasis: a safety and efficacy study of albendazole with ivermectin compared to treatment of single infection with bancroftian filariasis

BACKGROUND: In order to use a combination of ivermectin and albendazole for the elimination of lymphatic filariasis, it is important to assess the potential risk of increased adverse events in individuals infected with both lymphatic filariasis and onchocerciasis. We compared the safety and efficacy of albendazole (400 mg) in combination with ivermectin (150 micrograms/kg), for the treatment of co-infections of Wuchereria bancrofti and Onchocerca volvulus with single infection of W. bancrofti. METHODS: The safety study on co-infections was a crossover, double blind design, while for the single infection of bancroftian filariasis an open design comparing two treatments was used. For co-infection, one group was allocated a single dose of ivermectin (150 micrograms/kg) plus albendazole (400 mg) (Group A). The other group received placebo (Group B). Five days later the treatment regime was reversed, with the Group A receiving placebo and Group B receiving treatment. For the single bancroftian filariasis infection, one group received a single dose of albendazole (400 mg) plus ivermectin (150 microg/kg) (Group C) while the other group received a single dose of albendazole (400 mg) alone (Group D). Blood and skin specimens were collected on admission day, day 0, and on days 2, 3, and 7 to assess drug safety and efficacy. Thereafter, blood and skin specimens were collected during the 12 months follow up for the assessment of drug efficacy. Study individuals were clinically monitored every six hours during the first 48 hours following treatment, and routine clinical examinations were performed during the hospitalisation period and follow-up. RESULTS: In individuals co-infected with bancroftian filariasis and onchocerciasis, treatment with ivermectin and albendazole was safe and tolerable. Physiological indices showed no differences between groups with co-infection (W. bancrofti and O. volvulus) or single infection (W. bancrofti). The frequency of adverse events in co-infected individuals was 63% (5/8, Group A, albendazole + ivermectin) and 57% (4/7, Group B, placebo) and of mild or moderate intensity. In single W. bancrofti infection the frequency of adverse events was 50% (6/12, Group C, albendazole + ivermectin) and 38% (5/13, Group D, albendazole) and of a similar intensity to those experienced with co-infection. There were no differences in adverse events between treatment groups. There was no significant difference in the reduction of microfilaraemia following treatment with albendazole and ivermectin in groups with single or co-infection. CONCLUSION: Our findings suggest that ivermectin plus albendazole is a safe and tolerable treatment for co-infection of bancroftian filariasis and onchocerciasis.     

Randomized clinical trial on ivermectin versus thiabendazole for the treatment of strongyloidiasis

Background

Strongyloidiasis may cause a life-threatening disease in immunosuppressed patients. This can only be prevented by effective cure of chronic infections. Direct parasitologic exams are not sensitive enough to prove cure if negative. We used an indirect immune fluorescent antibody test (IFAT) along with direct methods for patient inclusion and efficacy assessment.

Methodology/Principal Findings

Prospective, randomized, open label, phase III trial conducted at the Centre for Tropical Diseases (Verona, Italy) to compare efficacy and safety of ivermectin (single dose, 200 µg/kg) and thiabendazole (two daily doses of 25 mg/Kg for two days) to cure strongyloidiasis. The first patient was recruited on 6^th December, 2004. Follow-up visit of the last patient was on 11^th January, 2007. Consenting patients responding to inclusion criteria were randomly assigned to one of the treatment arms. Primary outcome was: negative direct and indirect (IFAT) tests at follow-up (4 to 6 months after treatment) or subjects with negative direct test and drop of two or more IFAT titers. Considering 198 patients who concluded follow-up, efficacy was 56.6% for ivermectin and 52.2% for thiabendazole (p = 0.53). If the analysis is restricted to 92 patients with IFAT titer 80 or more before treatment (virtually 100% specific), efficacy would be 68.1% for ivermectin and 68.9% for thiabendazole (p = 0.93). Considering direct parasitological diagnosis only, efficacy would be 85.7% for ivermectin and 94.6% for thiabendazole (p = 0.21). In ivermectin arm, mild to moderate side effects were observed in 24/115 patients (20.9%), versus 79/108 (73.1%) in thiabendazole arm (p = 0.00).

Conclusion

No significant difference in efficacy was observed, while side effects were far more frequent in thiabendazole arm. Ivermectin is the drug of choice, but efficacy of single dose is suboptimal. Different dose schedules should be assessed by future, larger studies.

Trial Registration

Portal of Clinical Research with Medicines in Italy 2004–004693–87     

Treatment of tetanus: an open study to compare the efficacy of procaine penicillin and metronidazole.

A prospective, open, non-randomised clinical trial was carried out to compare the efficacy of procaine penicillin with metronidazole in the treatment of moderate tetanus among 173 patients. Patients in the metronidazole group had a significantly lower mortality rate, a shorter stay in hospital, and an improved response to treatment. These results establish the value of antimicrobial treatment in the management of tetanus and show that metronidazole is more efficacious than penicillin in this respect.     

Tribendimidine and albendazole for treating soil-transmitted helminths, Strongyloides stercoralis and Taenia spp.: open-label randomized trial

Background

Tribendimidine is an anthelminthic drug with a broad spectrum of activity. In 2004 the drug was approved by Chinese authorities for human use. The efficacy of tribendimidine against soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura) has been established, and new laboratory investigations point to activity against cestodes and Strongyloides ratti.

Methodology/Principal Findings

In an open-label randomized trial, the safety and efficacy of a single oral dose of albendazole or tribendimidine (both drugs administered at 200 mg for 5- to 14-year-old children, and 400 mg for individuals ≥15 years) against soil-transmitted helminths, Strongyloides stercoralis, and Taenia spp. were assessed in a village in Yunnan province, People''s Republic of China. The analysis was on a per-protocol basis and the trial is registered with controlled-trials.com (number ISRCTN01779485). Both albendazole and tribendimidine were highly efficacious against A. lumbricoides and, moderately, against hookworm. The efficacy against T. trichiura was low. Among 57 individuals who received tribendimidine, the prevalence of S. stercoralis was reduced from 19.3% to 8.8% (observed cure rate 54.5%, p = 0.107), and that of Taenia spp. from 26.3% to 8.8% (observed cure rate 66.7%, p = 0.014). Similar prevalence reductions were noted among the 66 albendazole recipients. Taking into account “new” infections discovered at treatment evaluation, which were most likely missed pre-treatment due to the lack of sensitivity of available diagnostic approaches, the difference between the drug-specific net Taenia spp. cure rates was highly significant in favor of tribendimidine (p = 0.001). No significant adverse events of either drug were observed.

Conclusions/Significance

Our results suggest that single-dose oral tribendimidine can be employed in settings with extensive intestinal polyparasitism, and its efficacy against A. lumbricoides and hookworm was confirmed. The promising results obtained with tribendimidine against S. stercoralis and Taenia spp. warrant further investigations. In a next step, multiple-dose schedules should be evaluated.     

Low omega-6 vs. low omega-6 plus high omega-3 dietary intervention for Chronic Daily Headache: Protocol for a randomized clinical trial

Background

Targeted analgesic dietary interventions are a promising strategy for alleviating pain and improving quality of life in patients with persistent pain syndromes, such as chronic daily headache (CDH). High intakes of the omega-6 (n-6) polyunsaturated fatty acids (PUFAs), linoleic acid (LA) and arachidonic acid (AA) may promote physical pain by increasing the abundance, and subsequent metabolism, of LA and AA in immune and nervous system tissues. Here we describe methodology for an ongoing randomized clinical trial comparing the metabolic and clinical effects of a low n-6, average n-3 PUFA diet, to the effects of a low n-6 plus high n-3 PUFA diet, in patients with CDH. Our primary aim is to determine if: A) both diets reduce n-6 PUFAs in plasma and erythrocyte lipid pools, compared to baseline; and B) the low n-6 plus high n-3 diet produces a greater decline in n-6 PUFAs, compared to the low n-6 diet alone. Secondary clinical outcomes include headache-specific quality-of-life, and headache frequency and intensity.

Methods

Adults meeting the International Classification of Headache Disorders criteria for CDH are included. After a 6-week baseline phase, participants are randomized to a low n-6 diet, or a low n-6 plus high n-3 diet, for 12 weeks. Foods meeting nutrient intake targets are provided for 2 meals and 2 snacks per day. A research dietitian provides intensive dietary counseling at 2-week intervals. Web-based intervention materials complement dietitian advice. Blood and clinical outcome data are collected every 4 weeks.

Results

Subject recruitment and retention has been excellent; 35 of 40 randomized participants completed the 12-week intervention. Preliminary blinded analysis of composite data from the first 20 participants found significant reductions in erythrocyte n-6 LA, AA and %n-6 in HUFA, and increases in n-3 EPA, DHA and the omega-3 index, indicating adherence.

Trial Registration

ClinicalTrials.gov (NCT01157208)

     

A randomized pilot trial of a full subsidy vs. a partial subsidy for obesity treatment

Intensive obesity treatment is mandated by federal health care reform but is costly. A partial subsidy for obesity treatment could lower the cost of treatment, without reducing its efficacy. This study sought to test whether a partial subsidy for obesity treatment would be feasible, as compared to a fully subsidized intervention. The study was a pilot randomized trial. Participants (n = 50) were primary care patients with obesity and at least one comorbid condition (diabetes, hypertension, dyslipidemia, or obstructive sleep apnea). Each participant received eight weight loss counseling visits as well as portion-controlled foods for weight loss. Participants were randomized to full subsidy or partial subsidy (2 vs. 1 meal per day provided). The primary outcome was weight change after 4 months. Secondary outcomes included changes in blood pressure, waist circumference, and health-related quality of life. Participants in the full and partial subsidy groups lost 5.9 and 5.3 kg, equivalent to 5.3% and 5.1% of initial weight, respectively (P = 0.71). Changes in secondary outcomes were similar in the two groups. A partial subsidy was feasible and induced a clinically similar amount of weight loss, compared to a full subsidy. Large-scale testing of economic incentives for weight control is merited given the federal mandate to offer weight loss counseling to obese patients.     

The in vitro effect of albendazole, ivermectin, diethylcarbamazine, and their combinations against infective third-stage larvae of nocturnally subperiodic Brugia malayi (Narathiwat strain): scanning electron microscopy.

Scanning electron microscopy (SEM) was employed to observe the effects of ivermectin (IVM), diethylcarbamazine (DEC), and albendazole (ALB) alone, and the drugs in combination (ALB+IVM and ALB+DEC) against infective third stage larvae (L3) of nocturnally subperiodic (NSP) Brugia malayi (Narathiwat strain) in vitro. IVM, at a concentration of 10(-4) M, killed L3 within 1-2 h. The SEM data showed damage to the L3 surface and loss of regular cuticular annulations. The cuticles were grooved in the middle region of the body. In comparison with normal L3 before treatment with IVM, the cuticular surface showed transversed striations with periodic annulations. The result demonstrated that IVM showed a larvicidal activity against L3 of NSP B. malayi cultivated in vitro. Compared with those larvae in the control group, the treated larvae had no morphological changes in the cuticular surface at the head, body, and tail regions after cultivation with all drugs alone, and in their combinations at a concentration of 10(-5) M for 7 d. In this system, and at that concentration, only the larvae cultured with ALB alone remained highly motile. Although no morphological changes had been observed by SEM, those drugs used alone (IVM and DEC) and in combinations (ALB+IVM and ALB+DEC), reduced larval motility throughout the experiments at a concentration of 10(-5) M. The minimum lethal concentration (MIC) of IVM against NSP B. malayi was 10(-4) M.     

Sulfadoxine-pyrimethamine-based combinations for malaria: a randomised blinded trial to compare efficacy, safety and selection of resistance in Malawi

Background

In Malawi, there has been a return of Plasmodium falciparum sensitivity to chloroquine (CQ) since sulfadoxine-pyrimethamine (SP) replaced CQ as first line treatment for uncomplicated malaria. When used for prophylaxis, Amodiaquine (AQ) was associated with agranulocytosis but is considered safe for treatment and is increasingly being used in Africa. Here we compare the efficacy, safety and selection of resistance using SP or CQ+SP or artesunate (ART)+SP or AQ+SP for the treatment of uncomplicated falciparum malaria.

Methodology and Findings

455 children aged 1–5 years were recruited into a double-blinded randomised trial comparing SP to the three combination therapies. Using intention to treat analysis with missing outcomes treated as successes, and without adjustment to distinguish recrudescence from new infections, the day 28 adequate clinical and parasitological response (ACPR) rate for SP was 25%, inferior to each of the three combination therapies (p<0.001). AQ+SP had an ACPR rate of 97%, higher than CQ+SP (81%) and ART+SP (70%), p<0.001. Nineteen children developed a neutropenia of ≤0.5×10³ cells/µl by day 14, more commonly after AQ+SP (p = 0.03). The mutation pfcrt 76T, associated with CQ resistance, was detected in none of the pre-treatment or post-treatment parasites. The prevalence of the pfmdr1 86Y mutation was higher after treatment with AQ+SP than after SP, p = 0.002.

Conclusions

The combination AQ+SP was highly efficacious, despite the low efficacy of SP alone; however, we found evidence that AQ may exert selective pressure for resistance associated mutations many weeks after treatment. This study confirms the return of CQ sensitivity in Malawi and importantly, shows no evidence of the re-emergence of pfcrt 76T after treatment with CQ or AQ. Given the safety record of AQ when used as a prophylaxis, our observations of marked falls in neutrophil counts in the AQ+SP group requires further scrutiny.

Trial Registration

Controlled-Trials.com ISRCTN22075368     

Open, randomized multicenter comparative trial of rabeprazole, ofloxacin and amoxicillin therapy for Helicobacter pylori eradication: 7 vs. 14 day treatment

BACKGROUND: Because of the increasing resistance to clarithromycin and metronidazole, two of the antibiotics used for the eradication of Helicobacter pylori, new therapeutic alternatives are needed. The aim of this study was to determine the efficacy of a randomized, comparative trial of 7 vs. 14-day triple treatment with rabeprazole, ofloxacin and amoxicillin for H. pylori eradication. MATERIAL AND METHODS: The present authors studied 76 dyspeptic patients infected with H. pylori diagnosed by both histology and a rapid urease test. Patients were randomized to receive rabeprazole (20 mg b.i.d.), plus ofloxacin (400 mg b.i.d.) and amoxicillin (1000 mg b.i.d.) for 7 days (group 1) vs. 14 days (group 2) and were followed by 6 weeks. Eradication was assessed 4 weeks after completing the course of study treatment by the (14)C-urea breath test. Per protocol and intention-to-treat eradication rates were determined. RESULTS: For the intention to treat analysis, the eradication rate was 62.2% for group 1 and 92.3% for group 2 (p =.004). For the per protocol analysis, eradication rate for group 1 was 63.9% and for group 2 was 97.3% (p =.001). CONCLUSIONS: Triple therapy with rabeprazole, amoxicillin and ofloxacin by 14 days was efficient for H. pylori eradication and therefore deserves further study. The same regimen prescribed for 7 days had a significantly lower and unacceptable cure rate and should not be used.     

Impact of two rounds of mass drug administration using diethylcarbamazine combined with albendazole on the prevalence of Brugia timori and of intestinal helminths on Alor Island, Indonesia

Background

Annual mass drug administration (MDA) using diethylcarbamizine (DEC, 6 mg/kg) combined with albendazole (alb, 400 mg) is recommended by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). This strategy has been shown to be efficient in the of control bancroftian filariasis, but data on brugian filariasis as well as on the positive side effects on intestinal helminths are lacking.

Methods

The effect of one selective treatment and two rounds of MDA using DEC and alb on the prevalence and intensity of Brugia timori infection were studied on Alor island using a cross-sectional and a cohort approach. Before the campaign and ten months after each treatment cycle microfilariae (mf) were assessed by filtration of night blood. Before and ten months after MDA, stool samples were collected and the prevalence of intestinal helminths were determined.

Results

In all, the mf-rate dropped from 26.8% before any treatment to 3.8% following the second MDA. Almost all mf-positive, treated individuals showed very low mf densities. The crude prevalence of hookworm dropped from 25.3% to 5.9%. The reduction of prevalence of Ascaris lumbricoides (32.3% to 27.6%) and Trichuris trichiura (9.4% to 8.9%) was less pronounced. Within a cohort of 226 individuals, which was examined annually, the prevalence of A. lumbricoides dropped from 43.8% to 26.5% and of T. trichiura from 12.8% to 6.6%. The results indicate that this MDA approach reduces not only the mf prevalence of B. timori but also the prevalence of hookworm and to a lesser extent also of A. lumbricoides and T. trichiura.

Conclusion

The MDA using DEC and alb as recommended by GPELF is extremely effective for areas with brugian filariasis. The beneficial effect of MDA on intestinal helminths may strengthen the national programme to eliminate lymphatic filariasis in Indonesia and may set resources free which are otherwise used for deworming campaigns of schoolchildren.     

A multi-center randomized trial to assess the efficacy of gatifloxacin versus ciprofloxacin for the treatment of shigellosis in Vietnamese children

Background

The bacterial genus Shigella is the leading cause of dysentery. There have been significant increases in the proportion of Shigella isolated that demonstrate resistance to nalidixic acid. While nalidixic acid is no longer considered as a therapeutic agent for shigellosis, the fluoroquinolone ciprofloxacin is the current recommendation of the World Health Organization. Resistance to nalidixic acid is a marker of reduced susceptibility to older generation fluoroquinolones, such as ciprofloxacin. We aimed to assess the efficacy of gatifloxacin versus ciprofloxacin in the treatment of uncomplicated shigellosis in children.

Methodology/Principal Findings

We conducted a randomized, open-label, controlled trial with two parallel arms at two hospitals in southern Vietnam. The study was designed as a superiority trial and children with dysentery meeting the inclusion criteria were invited to participate. Participants received either gatifloxacin (10 mg/kg/day) in a single daily dose for 3 days or ciprofloxacin (30 mg/kg/day) in two divided doses for 3 days. The primary outcome measure was treatment failure; secondary outcome measures were time to the cessation of individual symptoms. Four hundred and ninety four patients were randomized to receive either gatifloxacin (n  =  249) or ciprofloxacin (n  =  245), of which 107 had a positive Shigella stool culture. We could not demonstrate superiority of gatifloxacin and observed similar clinical failure rate in both groups (gatifloxacin; 12.0% and ciprofloxacin; 11.0%, p  =  0.72). The median (inter-quartile range) time from illness onset to cessation of all symptoms was 95 (66–126) hours for gatifloxacin recipients and 93 (68–120) hours for the ciprofloxacin recipients (Hazard Ratio [95%CI]  =  0.98 [0.82–1.17], p  =  0.83).

Conclusions

We conclude that in Vietnam, where nalidixic acid resistant Shigellae are highly prevalent, ciprofloxacin and gatifloxacin are similarly effective for the treatment of acute shigellosis.

Trial Registration

Controlled trials number ISRCTN55945881     

A prospective randomised trial to compare the efficacy and safety of hemabate and syntometrine for the prevention of primary postpartum haemorrhage

In a prospective, open-label, assessor-blind, randomised parallel group study the efficacy and safety of Hemabate (Pharmacia-Upjohn Pharmaceuticals, Milton Keynes, Buckinghamshire) an analogue of 15-methyl-prostaglandin (PGF2alpha) analogue was compared with Syntometrine (Alliance Pharmaceuticals, Chippenham, Wilts) the standard combination of ergometrine and syntocinon used for the active management of the third stage of labour and the prevention of primary postpartum haemorrhage (PPH). The study was set in a district general hospital with approximately 4,000 deliveries annually. The study was discontinued at the time of the interim analysis because of unacceptable gastrointestinal side effects. At the time of the interim analysis, a total of 529 women had completed the study with 263 randomised to receive PGF2alpha and 266 to receive ergometrine and syntocinon. In a pre-specified subgroup analysis, women delivered vaginally were further subdivided into those considered to be at high or low risk of primary PPH. The measured blood loss and incidence of PPH was similar in both treatment groups whether delivered by caesarean section or vaginally independent of whether women were considered to be at high or low risk. Adverse gastrointestinal events were recorded more often in the Hemabate group. The most common symptom was diarrhoea which occurred in 21% of women who received Hemabate compared to only 0.8% of Syntometrine users. PGF2alpha is as effective as Syntometrine in the prophylaxis of primary PPH in all groups studied but there was a statistically significantly increased risk of diarrhoea among users of PGF2alpha.     

Effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa in patients with mild to moderate hypertension: a controlled and randomized clinical trial.

In order to compare the antihypertensive effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa with captopril, a controlled and randomized clinical trial was done. Patients from 30 to 80 years old with diagnosed hypertension and without antihypertensive treatment for at least 1 month before were included. The experimental procedure consisted of the administration of an infusion prepared with 10 g of dry calyx from H. sabdariffa on 0.51 water (9.6 mg anthocyanins content), daily before breakfast, or captopril 25 mg twice a day, for 4 weeks. The outcome variables were tolerability, therapeutic effectiveness (diastolic reduction > or = 10 mm Hg) and, in the experimental group, urinary electrolytes modification. Ninety subjects were included, 15 withdrew from the study due to non-medical reasons; so, the analysis included 39 and 36 patients from the experimental and control group, respectively. The results showed that H. sabdariffa was able to decrease the systolic blood pressure (BP) from 139.05 to 123.73mm Hg (ANOVA p < 0.03) and the diastolic BP from 90.81 to 79.52mm Hg (ANOVA p < 0.06). At the end of the study, there were no significant differences between the BP detected in both treatment groups (ANOVA p > 0.25). The rates of therapeutic effectiveness were 0.7895 and 0.8438 with H. sabdariffa and captopril, respectively (chi2, p > 0.560), whilst the tolerability was 100% for both treatments. A natriuretic effect was observed with the experimental treatment. The obtained data confirm that the H. sabdariffa extract, standardized on 9.6mg of total anthocyanins, and captopril 50 mg/day, did not show significant differences relative to hypotensive effect, antihypertensive effectiveness, and tolerability.     

Echinaforce and other Echinacea fresh plant preparations in the treatment of the common cold. A randomized, placebo controlled, double-blind clinical trial.

The aim of this randomized, double-blind, placebo controlled study was to investigate the efficacy and safety of different doses and preparations of Echinacea purpurea in the treatment of common cold. 246 of 559 recruited healthy, adult volunteers caught a common cold and took 3 times daily 2 tablets of either Echinaforce (Echinacea purpurea-preparation from 95% herba and 5% radix), Echinacea purpurea concentrate (same preparation at 7 times higher concentration), special Echinacea purpurea radix preparation (totally different from that of Echinaforce) or placebo until they felt healthy again but not longer than 7 days. The primary endpoint was the relative reduction of the complaint index defined by 12 symptoms during common cold according to the doctor's record. Echinaforce and its concentrated preparation were significantly more effective than the special Echinacea extract or placebo. All treatments were well tolerated. Among the Echinacea groups the frequency of adverse events was not significantly higher than in the placebo group. Therefore, Echinacea concentrate as well as Echinaforce represent a low-risk and effective alternative to the standard symptomatic medicines in the acute treatment of common cold.