Antihypertensive efficacy and tolerability of candesartan-hydrochlorothiazide 32/12.5 mg and 32/25 mg in patients not optimally controlled with candesartan monotherapy

Aim. To evaluate the efficacy and tolerability of candesartan cilexetil 32 mg in combination with hydrochlorothiazide (HCT) 12.5 mg or 25 mg in hypertensive patients not optimally controlled with candesartan monotherapy. Patients and methods. A total of 3521 patients with treated or untreated hypertension and sitting diastolic blood pressure (DBP) 90-114 mmHg, entered a single-blind run-in phase with candesartan (16 mg for 2 weeks, followed by 32 mg for 6 weeks). At the end of the run-in phase, 1975 patients who still had DBP 90-114 mmHg were randomized to 8 weeks' double-blind treatment with either candesartan 32 mg (n=654), or candesartan-HCT 32/12.5 mg (n=656), or candesartan-HCT 32/25 mg (n=665). Principal results. At randomization, the mean blood pressure was similar in the three treatment groups (approximately 153/97 mmHg). It was reduced during the double-blind treatment phase by 6.1/5.6 mmHg in the candesartan 32 mg group, by 13.0/8.8 mmHg in the candesartan-HCT 32/12.5 mg group, and by 15.5/10.0 mmHg in the candesartan-HCT 32/25 mg group (p < 0.01 for all between treatment comparisons). All study treatments were generally well tolerated. Conclusion. Candesartan-HCT 32/12.5 mg and candesartan-HCT 32/25 mg are highly effective and provide improved blood pressure reduction and blood pressure control relative to candesartan 32 mg monotherapy, with maintained tolerability, in hypertensive patients whose blood pressure is not optimally controlled with candesartan monotherapy. Furthermore, candesartan-HCT 32/25 mg is more effective than candesartan-HCT 32/12.5 mg in this population

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)