Aprepitant versus ondansetron in preoperative triple-therapy treatment of nausea and vomiting in neurosurgery patients: study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: The incidence of postoperative nausea and vomiting is 50% to 80% after neurosurgery. The common prophylactic treatment for postoperative nausea and vomiting is a triple therapy of droperidol (Inapsine), promethazine (Phenergan) and dexamethasone (Decadron). Newer, more effectives methods of prophylaxis are being investigated. We designed this prospective, double-blind, single center study to compare the efficacy of ondansetron (Zofran) to a neurokinin-1 antagonist, aprepitant (Emend), as a substitute for droperidol, in the prophylactic treatment of postoperative nausea and vomiting after neurosurgery. METHODS: After obtaining institutional review board approval, One hundred-seventy-six patients, 18-85 years of age with ASA I to III, who did not receive anti-emetics 24 hours before surgery and are expected to undergo general anesthesia for neurosurgery lasting longer than two hours were included in this study. After meeting the inclusion and exclusion criteria and providing written informed consent, patients will be randomly assigned in a 1:1 ratio to one of two treatment groups: aprepitant or ondansetron. Because ondansetron is given intravenously and aprepitant orally, patients will be given an oral or intravenous placebo to maintain the double blind. Patients will receive aprepitant 40 mg PO/placebo within 2 hours prior to induction. At induction, a combination of intravenous dexamethasone 10 mg, promethazine 25 mg and ondansetron 4 mg/placebo will be given. The primary outcome measures are the episodes and severity of nausea and vomiting; administration of rescue antiemetic; and opioid consumption for 120 hours postoperatively. Standard safety assessments will include adverse event reports, physical and laboratory data, awakening time and duration of recovery from anesthesia. Logistic regression will be used to test the efficacy of aprepitant compared to ondansetron with demographic characteristics as potential covariates in the model. For the number of rescue therapy treatments used during the postoperative period, a Wilcoxon rank sum test will be performed. DISCUSSION: The results of this comparative study will potentially identify an improved treatment regimen that will decrease the incidence and severity of postoperative nausea and vomiting in patients undergoing neurosurgery. This will serve to enhance patient recovery and overall satisfaction of neurosurgical patients in the immediate postoperative period. Registered at The Ohio State University Biomedical Sciences Institutional Review Board: Protocol Number: 2007H0053 KEYWORDS: aprepitant, postoperative nausea and vomiting, craniotomy, ondansetron. Word Count: 347.     

Nonadherence to treatment protocol in published randomised controlled trials: a review

ABSTRACT: This review aimed to ascertain the extent to which nonadherence to treatment protocol is reported and addressed in a cohort of published analyses of randomised controlled trials (RCTs). One hundred publications of RCTs, randomly selected from those published in BMJ, New England Journal of Medicine, the Journal of the American Medical Association and The Lancet during 2008, were reviewed to determine the extent and nature of reported nonadherence to treatment protocol, and whether statistical methods were used to examine the effect of such nonadherence on both benefit and harms analyses. We also assessed the quality of trial reporting of treatment protocol nonadherence and the quality of reporting of the statistical analysis methods used to investigate such nonadherence. Nonadherence to treatment protocol was reported in 98 of the 100 trials, but reporting on such nonadherence was often vague or incomplete. Forty-two publications did not state how many participants started their randomised treatment. Reporting of treatment initiation and completeness was judged to be inadequate in 64% of trials with short-term interventions and 89% of trials with long-term interventions. More than half (51) of the 98 trials with treatment protocol nonadherence implemented some statistical method to address this issue, most commonly based on per protocol analysis (46) but often labelled as intention to treat (ITT) or modified ITT (23 analyses in 22 trials). The composition of analysis sets for their benefit outcomes were not explained in 57% of trials, and 62% of trials that presented harms analyses did not define harms analysis populations. The majority of defined harms analysis populations (18 out of 26 trials, 69%) were based on actual treatment received, while the majority of trials with undefined harms analysis populations (31 out of 43 trials, 72%) appeared to analyse harms using the ITT approach. Adherence to randomised intervention is poorly considered in the reporting and analysis of published RCTs. The majority of trials are subject to various forms of nonadherence to treatment protocol, and though trialists deal with this nonadherence using a variety of statistical methods and analysis populations, they rarely consider the potential for bias introduced. There is a need for increased awareness of more appropriate causal methods to adjust for departures from treatment protocol, as well as guidance on the appropriate analysis population to use for harms outcomes in the presence of such nonadherence.     

Treatment of established postoperative nausea and vomiting: a quantitative systematic review

Background  

The relative efficacy of antiemetics for the treatment of postoperative nausea and vomiting (PONV) is poorly understood.     

Measuring quality of life in clinical trials: a taxonomy and review.

Measurement of quality of life is becoming increasingly relevant to controlled clinical trials. Two basic types of instrument are available: generic instruments, which include health profiles and utility measurements based on the patient''s preferences in regard to treatment and outcome; and specific instruments, which focus on problems associated with individual diseases, patient groups or areas of function. The two approaches are not mutually exclusive; each has its strengths and weaknesses and may be suitable under different circumstances. We surveyed 75 randomized trials published in three medical journals in 1986 and categorized them according to the importance of quality of life as a measure of outcome and the extent to which quality of life was actually measured. Although a number of the investigators used quality-of-life instruments in a sophisticated manner, in only 10 of 55 trials in which the measurement had been judged to be crucial or important were instruments with established validity and responsiveness used. We conclude that although accurate measurement of quality of life in randomized trials is now feasible it is still not widely done. Using the framework we have outlined, investigators can choose generic or specific instruments according to the purpose and the focus of their trial.     

Effect of preventive treatment for tuberculosis in adults infected with HIV: systematic review of randomised placebo controlled trials

Objective: To determine whether preventive treatment for tuberculosis in adults infected with HIV reduces the frequency of tuberculosis and overall mortality. Design: Systematic review and data synthesis of randomised placebo controlled trials. Main outcome measures: Active tuberculosis, mortality, and adverse drug reaction requiring cessation of the study regimen. Outcomes stratified by status of purified protein derivative skin test. Results: Four trials comprising 4055 adults from Haiti, Kenya, the United States, and Uganda were included. All compared isoniazid (6-12 months) with placebo, and one trial also compared multidrug treatment for 3 months with placebo. Mean follow up was 15-33 months. Overall, frequency of tuberculosis (relative risk 0.57, 95% confidence interval 0.41 to 0.79) was reduced in those receiving preventive treatment compared with placebo: mortality was not significantly reduced (0.93, 0.83 to 1.05). In subjects positive for purified protein derivative receiving preventive treatment, the risk of tuberculosis was reduced substantially (0.32, 0.19 to 0.51) and the risk of death was reduced moderately (0.73, 0.57 to 0.95) compared with those taking placebo. In adults negative for purified protein derivative receiving preventive treatment, the risk of tuberculosis (0.82, 0.50 to 1.36) and the risk of death (1.02, 0.89 to 1.17) were not reduced significantly. Adverse drug reactions were more frequent, but not significantly so, in patients receiving drug compared with placebo (1.45, 0.98 to 2.14). Conclusions: Preventive treatment given for 3-12 months protects against tuberculosis in adults infected with HIV, at least in the short to medium term. Protection is greatest in subjects positive for purified protein derivative, in whom death is also less frequent. Long term benefits remain to be shown.

Key messages

• One third of the world’s population is infected with Mycobacterium tuberculosis
• People infected with HIV are at much increased risk of developing active tuberculosis
• Short term preventive drug treatment given to people infected with HIV reduces the occurrence of active tuberculosis
• The benefit is greatest in people with latent infection, as shown by a positive skin test for tuberculosis, and this group also exhibits a survival benefit

     

Herbal remedies for anxiety - a systematic review of controlled clinical trials.

Anxiety is a prominent indication for herbal medicine. This systematic review was therefore aimed at summarising the evidence for or against the anxiolytic efficacy of such treatments. Six databases were searched for all randomised clinical trials testing herbal monopreparations in the alleviation of anxiety. Seven such studies and one systematic review were located. Eight different herbals were studied. The herbal medicines, which, according to these data are associated with anxiolytic activity in humans, are Piper methysticum and Bacopa monniera. Only for kava were independent replications available. It was concluded that there is a lack of rigorous studies in this area and that only kava has been shown beyond reasonable doubt to have anxiolytic effects in humans.     

Human plasma quantification of droperidol and ondansetron used in preventing postoperative nausea and vomiting with a LC/ESI/MS/MS method

An analytical method based upon liquid chromatography coupled to ion trap mass spectrometry (MS) detection with electrospray ionization interface has been developed for the simultaneous identification and quantification of droperidol and ondansetron in human plasma. The two drugs were isolated from 0.5 mL of plasma using a basic liquid-liquid extraction with diethyl ether/heptane (90/10, v/v) and tropisetron and haloperidol as internal standards, with satisfactory extraction recoveries. They were separated on a 5-μm C(18) Highpurity column (150 mm×2.1 mm I.D.) maintained at 30°C. The elution was achieved isocratically with a mobile phase of 2 mM HCOONH(4) pH 3.8 buffer/acetonitrile (60/40, v/v) at a flow rate of 200 μL/min. Data were collected either in full-scan MS mode at m/z 100-450 or in full-scan MS-MS mode, selecting the [M+H] (+) ion at m/z=294.0 for ondansetron, m/z=285.2 for tropisetron, m/z=380.0 for droperidol and m/z=376.0 for haloperidol. The most intense daughter ion of ondansetron (m/z=212.0) and droperidol (m/z=194.0) were used for quantification. Retention times for tropisetron, ondansetron, droperidol and haloperidol were 2.50, 2.61, 3.10 and 4.68 min, respectively. Calibration curves were linear for both compounds in the 0.50-500 ng/mL range. The limits of detection and quantification were 0.10 ng/mL and 0.50 ng/mL, respectively. The intra- and inter-assay precisions were lower than 6.4% and intra- and inter-assay recoveries were in the 97.6-101.9% range for the three 3, 30 and 300 ng/mL concentrations. This method allows simultaneous and rapid measurement of droperidol and ondansetron, which are frequently co-administrated for the prevention of postoperative nausea and vomiting.     

Anesthesiologists' practice patterns for treatment of postoperative nausea and vomiting in the ambulatory Post Anesthesia Care Unit

Background

Induction of the COX-2 isoenzyme appears to play a major role in the genesis of central sensitization after nociceptive stimulation. This study aimed to investigate the efficacy of a single, oral dose of the specific COX-2 inhibitor-valdecoxib in attenuating the central sensitization – induced secondary hyperalgesia in a heat/capsaicin pain model in healthy volunteers.

Methods

The study was a randomized, double blind, placebo controlled, crossover, single dose efficacy trial using 20 healthy volunteers. Two hours following placebo or 40 mg, PO valdecoxib, participants underwent skin sensitization with heat/capsaicin, as well as supra-threshold pain and re-kindling measurements according to an established, validated pain model. Subjects rated pain intensity and unpleasantness on a visual analog scale and the area of secondary hyperalgesia was serially mapped.

Results

The area of secondary hyperalgesia produced after 40 mg of valdecoxib was no different than that after placebo. Furthermore, there were no significantly relevant differences when volunteers were treated with valdecoxib or placebo in relation to either cold- or hot pain threshold or the intensity of pain after supra-threshold, thermal pain stimulation.

Conclusion

We demonstrated that a single, oral dose of valdecoxib when does not attenuate secondary hyperalgesia induced by heat/capsaicin in a cutaneous sensitization pain model in healthy volunteers.     

Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review

ObjectiveTo quantify the antiemetic efficacy and adverse effects of cannabis used for sickness induced by chemotherapy.DesignSystematic review.Studies30 randomised comparisons of cannabis with placebo or antiemetics from which dichotomous data on efficacy and harm were available (1366 patients). Oral nabilone, oral dronabinol (tetrahydrocannabinol), and intramuscular levonantradol were tested. No cannabis was smoked. Follow up lasted 24 hours.ResultsCannabinoids were more effective antiemetics than prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone, or alizapride: relative risk 1.38 (95% confidence interval 1.18 to 1.62), number needed to treat 6 for complete control of nausea; 1.28 (1.08 to 1.51), NNT 8 for complete control of vomiting. Cannabinoids were not more effective in patients receiving very low or very high emetogenic chemotherapy. In crossover trials, patients preferred cannabinoids for future chemotherapy cycles: 2.39 (2.05 to 2.78), NNT 3. Some potentially beneficial side effects occurred more often with cannabinoids: “high” 10.6 (6.86 to 16.5), NNT 3; sedation or drowsiness 1.66 (1.46 to 1.89), NNT 5; euphoria 12.5 (3.00 to 52.1), NNT 7. Harmful side effects also occurred more often with cannabinoids: dizziness 2.97 (2.31 to 3.83), NNT 3; dysphoria or depression 8.06 (3.38 to 19.2), NNT 8; hallucinations 6.10 (2.41 to 15.4), NNT 17; paranoia 8.58 (6.38 to 11.5), NNT 20; and arterial hypotension 2.23 (1.75 to 2.83), NNT 7. Patients given cannabinoids were more likely to withdraw due to side effects 4.67 (3.07 to 7.09), NNT 11.ConclusionsIn selected patients, the cannabinoids tested in these trials may be useful as mood enhancing adjuvants for controlling chemotherapy related sickness. Potentially serious adverse effects, even when taken short term orally or intramuscularly, are likely to limit their widespread use.

What is already known on this topic

Requests have been made for legalisation of cannabis (marijuana) for medical useLong term smoking of cannabis can have physical and neuropsychiatric adverse effectsCannabis may be useful in the control of chemotherapy related sickness

What this study adds

Oral nabilone and dronabinol and intramuscular levonantradol are superior to conventional antiemetics (such as prochlorperazine or metoclopramide) in chemotherapySide effects are common with cannabinoids, and although some may be potentially beneficial (euphoria, “high,” sedation), others are harmful (dysphoria, depression, hallucinations)Many patients have a strong preference for cannabinoids     

Quantitative systematic review of randomised controlled trials comparing antibiotic with placebo for acute cough in adults

Objectives: To assess whether antibiotic treatment for acute cough is effective and to measure the side effects of such treatment. Design: Quantitative systematic review of randomised placebo controlled trials. Data sources: Nine trials (8 published, 1 unpublished) retrieved from a systematic search (electronic databases, contact with authors, contact with drug manufacturers, reference lists); no restriction on language. Main outcome measures: Proportion of subjects with productive cough at follow up (7-11 days after consultation with general practitioner); proportion of subjects who had not improved clinically at follow up; proportion of subjects who reported side effects from taking antibiotic or placebo. Results: Eight trials contributed to the meta-analysis. Resolution of cough was not affected by antibiotic treatment (relative risk 0.85 (95% confidence interval 0.73 to 1.00)), neither was clinical improvement at re-examination (relative risk 0.62 (0.36 to 1.09)). The side effects of antibiotic were more common in the antibiotic group when compared to placebo (relative risk 1.51 (0.86 to 2.64)). Conclusions: Treatment with antibiotic does not affect the resolution of cough or alter the course of illness. The benefits of antibiotic treatment are marginal for most patients with acute cough and may be outweighed by the side effects of treatment.

Key messages

• Acute cough, with or without sputum, is a common reason for consulting a general practitioner
• Although antibiotic treatment is common for this condition, its likely benefits and side effects have not been measured
• This systematic review reports the outcome of nine randomised controlled trials that compared antibiotic with placebo in patients with acute cough
• Resolution of cough and clinical improvement at follow up was no different in the two groups
• The benefits of antibiotic treatment seem to be marginal for most patients with acute cough and may be outweighed by the side effects of treatment

     

Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression.

OBJECTIVE--A comprehensive meta-analysis of clinical trial data was performed to assess the possible association of fluoxetine and suicidality (suicidal acts and ideation). DESIGN--Retrospective analysis of pooled data from 17 double blind clinical trials in patients with major depressive disorder comparing fluoxetine (n = 1765) with a tricyclic antidepressant (n = 731) or placebo (n = 569), or both. MAIN OUTCOME MEASURES--Multiple data sources were searched to identify patients with suicidal acts. Suicidal ideation was assessed with item 3 of the Hamilton depression rating scale, which systematically rates suicidality. Emergence of substantial suicidal ideation was defined as a change in the rating of this item from 0 or 1 at baseline to 3 or 4 during double blind treatment; worsening was defined as any increase from baseline; improvement was defined as a decrease from baseline at the last visit during the treatment. RESULTS--Suicidal acts did not differ significantly in comparisons of fluoxetine with placebo (0.2% v 0.2%, p = 0.494, Mantel-Haenszel adjusted incidence difference) and with tricyclic antidepressants (0.7% v 0.4%, p = 0.419). The pooled incidence of suicidal acts was 0.3% for fluoxetine, 0.2% for placebo, and 0.4% for tricyclic antidepressants, and fluoxetine did not differ significantly from either placebo (p = 0.533, Pearson''s chi 2) or tricyclic antidepressants (p = 0.789). Suicidal ideation emerged marginally significantly less often with fluoxetine than with placebo (0.9% v 2.6%, p = 0.094) and numerically less often than with tricyclic antidepressants (1.7% v 3.6%, p = 0.102). The pooled incidence of emergence of substantial suicidal ideation was 1.2% for fluoxetine, 2.6% for placebo, and 3.6% for tricyclic antidepressants. The incidence was significantly lower with fluoxetine than with placebo (p = 0.042) and tricyclic antidepressants (p = 0.001). Any degree of worsening of suicidal ideation was similar with fluoxetine and placebo (15.4% v 17.9%, p = 0.196) and with fluoxetine and tricyclic antidepressants (15.6% v 16.3%, p = 0.793). The pooled incidence of worsening of suicidal ideation was 15.3% for fluoxetine, 17.9% for placebo, and 16.3% for tricyclic antidepressants. The incidence did not differ significantly with fluoxetine and placebo (p = 0.141) or tricyclic antidepressants (p = 0.542). Suicidal ideation improved significantly more with fluoxetine than with placebo (72.0% v 54.8%, p less than 0.001) and was similar to the improvement with tricyclic antidepressants (72.5% v 69.8%, p = 0.294). The pooled incidence of improvement of suicidal ideation was 72.2% for fluoxetine, 54.8% for placebo, and 69.8% for tricyclic antidepressants. The incidence with fluoxetine was significantly greater than with placebo (p less than 0.001) and did not differ from that with tricyclic antidepressants (p = 0.296). CONCLUSIONS--Data from these trials do not show that fluoxetine is associated with an increased risk of suicidal acts or emergence of substantial suicidal thoughts among depressed patients.     

Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials

Background:

Results of randomized controlled trials evaluating zinc for the treatment of the common cold are conflicting. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zinc for such use.

Methods:

We searched electronic databases and other sources for studies published through to Sept. 30, 2011. We included all randomized controlled trials comparing orally administered zinc with placebo or no treatment. Assessment for study inclusion, data extraction and risk-of-bias analyses were performed in duplicate. We conducted meta-analyses using a random-effects model.

Results:

We included 17 trials involving a total of 2121 participants. Compared with patients given placebo, those receiving zinc had a shorter duration of cold symptoms (mean difference −1.65 days, 95% confidence interval [CI] −2.50 to −0.81); however, heterogeneity was high (I² = 95%). Zinc shortened the duration of cold symptoms in adults (mean difference −2.63, 95% CI −3.69 to −1.58), but no significant effect was seen among children (mean difference −0.26, 95% CI −0.78 to 0.25). Heterogeneity remained high in all subgroup analyses, including by age, dose of ionized zinc and zinc formulation. The occurrence of any adverse event (risk ratio [RR] 1.24, 95% CI 1.05 to 1.46), bad taste (RR 1.65, 95% CI 1.27 to 2.16) and nausea (RR 1.64, 95% CI 1.19 to 2.27) were more common in the zinc group than in the placebo group.

Interpretation:

The results of our meta-analysis showed that oral zinc formulations may shorten the duration of symptoms of the common cold. However, large high-quality trials are needed before definitive recommendations for clinical practice can be made. Adverse effects were common and should be the point of future study, because a good safety and tolerance profile is essential when treating this generally mild illness.The common cold is a frequent respiratory infection experienced 2 to 4 times a year by adults and up to 8 to 10 times a year by children.^1–3 Colds can be caused by several viruses, of which rhinoviruses are the most common.⁴ Despite their benign nature, colds can lead to substantial morbidity, absenteeism and lost productivity.^5–7Zinc, which can inhibit rhinovirus replication and has activity against other respiratory viruses such as respiratory syncytial virus,⁸ is a potential treatment for the common cold. The exact mechanism of zinc’s activity on viruses remains uncertain. Zinc may also reduce the severity of cold symptoms by acting as an astringent on the trigeminal nerve.^9,10A recent meta-analysis of randomized controlled trials concluded that zinc was effective at reducing the duration and severity of common cold symptoms.¹¹ However, there was considerable heterogeneity reported for the primary outcome (I² = 93%), and subgroup analyses to explore between-study variations were not performed. The efficacy of zinc therefore remains uncertain, because it is unknown whether the variability among studies was due to methodologic diversity (i.e., risk of bias and therefore uncertainty in zinc’s efficacy) or differences in study populations or interventions (i.e., zinc dose and formulation).We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zinc for the treatment of the common cold. We sought to improve upon previous systematic reviews^11–17 by exploring the heterogeneity with subgroups identified a priori, identifying new trials by instituting a broader search and obtaining additional data from authors.     

Reporting quality of randomized controlled trials in patients with HIV on antiretroviral therapy: a systematic review

Background

To allow for correct evaluation of clinical trial results, readers require comprehensive, clear, and highly transparent information on the methodology used and the results obtained. This study aimed to evaluate the quality of reporting in articles on randomized controlled trials (RCTs) of antiretroviral therapy (ART) in the field of HIV/AIDS.

Methods

We searched for original articles on RCTs of ART developed in the field of HIV/AIDS in PubMed database by 5 April 2016. Searched articles were divided into three groups based on the revision year in which the Consolidated Standards of Reporting Trials (CONSORT) guidelines were published: Period 1 (1996–2001); Period 2 (2002–2010); and Period 3 (2011–2016). We evaluated the articles using the reporting rates of the 37 items in the CONSORT 2010 checklist, five items in the protocol deviation, and the three items in the ethics.

Results

Fifty-two articles were extracted and included in this study. Many of the reporting rates calculated using the CONSORT 2010 checklist showed a significantly increasing trend over the successive periods (65% in Period 1, 67% in Period 2, 79% in Period 3; p?<?0.0001). The items with reporting rates?<?50% were “the presence or absence of a protocol change and the reason for such a change,” “randomization and blinding,” and “where the full trial protocol can be accessed.” Reporting rates of deviations were as low as?<?30%, while the reporting rates for patient compliance were the highest (>80% in Period 3) among the five items. The reporting rates for obtaining informed consent and approval by the ethics committee or institutional review board were high (>88%), regardless of the time period assessed.

Conclusion

In terms of representative RCT articles in the field of HIV/AIDS, the reporting rate of the items defined by CONSORT was approximately 70%, improving over the successive CONSORT statement revision periods.

     

Registered clinical trials investigating treatment with cell-derived extracellular vesicles: a scoping review

Background aimsInterest in cell-based therapy using extracellular vesicles (EVs) is intensifying, building upon promising preclinical research and a handful of published clinical studies. Registered clinical trials remain small, heterogeneous in design and underpowered to determine safety and efficacy on their own. A scoping review of registered studies can identify opportunities to pool data and perform meta-analysis.MethodsRegistered trials were identified by searching clinical trial databases (Clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform and the Chinese Clinical Trial Registry) on June 10, 2022.ResultsSeventy-three trials were identified and included for analysis. Mesenchymal stromal cells (MSCs) were the most common cell type from which EVs were derived (49 studies, 67%). Among the 49 identified MSC-EV studies, 25 were controlled trials (51%) with a combined total of 3094 participants anticipated to receive MSC-derived EVs (2225 in controlled studies). Although EVs are being administered to treat a broad range of conditions, trials treating patients with coronavirus disease-2019 and/or acute respiratory distress syndrome were observed most commonly. Despite heterogeneity between studies, we anticipate that at least some of the studies could be combined in meaningful meta-analysis and that a combined sample size of 1000 patients would provide the ability to detect a ≥5% difference in mortality with MSC-EVs compared to controls and could be achieved by December 2023.ConclusionsThis scoping review identifies potential barriers that may stall clinical translation of EV-based treatment, and our analysis calls for more standardized product characterization, use of quantifiable product quality attributes and consistent outcome reporting in future clinical trials.