Background Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely used in clinical practice. The safety and efficacy of these agents in peritoneal dialysis (PD) patients are unclear. Objectives We conducted a systematic review to study the safety and efficacy of ACEI and ARB use in PD patients. Primary outcome measures were mortality and cardiovascular (CV) events; secondary outcome measures were renal function, proteinuria, hyperkalemia, and erythropoietin requirement at 3 months. Methods We searched Medline, EMBASE, Cochrane Central Register of Controlled Trials, trial registry Web sites, reference lists of eligible and review articles, as well as abstracts from the American Society of Nephrology and Canadian Society of Nephrology meetings. To be eligible, studies had to be randomized controlled trials that allocated PD patients to ACEI and ARB use or to placebo or other antihypertensive medications, included adult patients, and reported on at least one of the outcome measures. Results 418 citations were identified. Four met the eligibility criteria. Three examined CV events and mortality, of which two studies did not have any events. The third showed no statistically significant difference between control and treatment groups in either CV events or mortality: odds ratio 1.56 [95% confidence interval (CI) 0.24 – 10.05] for mortality and odds ratio 1.00 (95% CI 0.19 – 5.40) for CV events. Two studies reported renal function at 12 months and the weighted mean difference was 0.91 mL/minute/1.73 m2 (95% CI 0.14 – 1.68), favoring ACEI and ARB use. Conclusions In PD patients, evidence for the use of ACEIs and ARBs for reduction of mortality and CV events is lacking. Limited data suggest that they slow the loss of residual renal function.

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Background Postoperative atrial fibrillation (POAF) is a frequent adverse event after thoracic surgery with associated morbidity, mortality, and healthcare costs. It has been shown to be preventable with prophylactic amiodarone, which is only recommended in high-risk individuals due to the potential associated side effects. Risk factors for POAF have been identified and incorporated into a prediction model to identify high-risk patients. Further evaluation in the form of a multicenter clinical trial is required to assess the effectiveness of prophylaxis specifically in this high-risk population. The feasibility of such a trial first needs to be assessed. Methods The PREP-AF trial is a double-blind randomized controlled feasibility trial. Individuals undergoing major thoracic surgery who are identified to be high-risk by the POAF prediction model will be randomized 1:1 to receive a short course of amiodarone vs. placebo in the immediate postoperative period. The primary outcome is feasibility, which will be measured by the number of eligible patients identified, consented, and randomized; intervention adherence; and measurement of future outcomes of a full trial. Discussion This study will determine the feasibility of a randomized controlled trial to assess the effectiveness of prophylactic amiodarone, in high-risk patients undergoing major thoracic surgery. This will inform the development of a multi-center trial to establish if prophylactic amiodarone is safe and effective at reducing the incidence of POAF. Preventing this adverse event will not only improve outcomes for patients but also reduce the associated health resource utilization and costs. Trial registration ClinicalTrials.gov NCT04392921. Registered on 19 May 2020.

Multicentric approaches are widely used in clinical trials to assess generalizability of findings, however they are novel in preclinical experimentation. We synthesized characteristics of multilaboratory studies and quantitatively compared them to single laboratory studies. We systematically identified sixteen in vivo interventional multilaboratory studies and matched them to 100 single laboratory studies by intervention and disease. Differences in standardized mean differences (DSMD) were calculated to compare treatment effects based on study design. The multilaboratory study design was applied across a range of diseases (e.g. stroke, diabetes, trauma). The median number of labs was 4 (range 2-6) and the median sample size was 111 (range 23-384). Multilaboratory studies adhered to practices that reduce risk of bias and were transparently reported. These studies demonstrated significantly smaller treatment effects than single lab studies (DSMD 0.72 [95% confidence interval 0.43-1]). Preclinical multilaboratory studies demonstrate trends that have been well recognized in clinical research (i.e. smaller treatment effects with greater rigour in study design). This approach may provide a method to robustly assess interventions and reproducibility of findings between laboratories.

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