Protocol version 5, 5 October 2018
Protocol version 5, 5 October 2018. reduced left ventricular ejection fraction (HFrEF) with an ejection fraction ?40% on optimal therapy recruited from specialized HF clinics in Denmark. The primary aim is to investigate the effect of the SGLT2 inhibitor empagliflozin on N-terminal pro-brain natriuretic peptide (NT-proBNP). Secondary endpoints include cardiac biomarkers, function and hemodynamics, metabolic and renal parameters, daily activity level, and quality of life. Patients are assigned 1:1 to 90?days treatment with empagliflozin 10?mg daily or placebo. Patients with T2D are required to be on recommended doses of anti-glycemic therapy with a hemoglobin A1c (HbA1c) of 6.5C10.0% (48C86?mmol/mol). To show a between-group difference in the change of NT-proBNP of 30%, a total of 189 patients will be included. Discussion The Empire HF trial will elucidate the effects and modes of action of empagliflozin in HFrEF patients with and without T2D and provide important mechanistic data which will complement ongoing event-driven trials. Trial registration Clinicaltrialsregister.eu, EudraCT Number 2017-001341-27. Registered on 29 May 2017. ClinicalTrials.gov, “type”:”clinical-trial”,”attrs”:”text”:”NCT03198585″,”term_id”:”NCT03198585″NCT03198585. Registered on 26 June 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3474-5) contains supplementary material, which is available to authorized users. ventricular tachycardia, value ?0.05 is CUDC-101 considered statistically significant. Normally distributed variables will be presented as mean??standard deviation (SD) and skewed distributed variables as median and interquartile range [IQR]. Comparisons between treatment and placebo group will be performed by an unpaired CUDC-101 two sample laying down the principles and guidelines of good manufacturing practice and in compliance with (The allocation sequence is generated by Glostrup Pharmacy using computer-generated random numbers in blocks of 10. Treatment CUDC-101 may be unblinded in medical emergencies during CUDC-101 the study if the investigators deem it necessary. Unblinding during the study period may be made individually and is performed by telephone contact from the investigators to Glostrup Pharmacy, where the allocation sequence is stored. A copy of the allocation sequence is concealed in opaque, sealed envelopes which are stored in a locked cabinet in the sponsors office. Data analysis will be blinded to the Rabbit Polyclonal to KLF10/11 investigators regarding primary, exploratory, and secondary endpoints (triple blinding). Study organization Study centers and time schedulePatients are recruited from specialized HF clinics at five sites in Denmark (Herlev-Gentofte Hospital, Odense University Hospital, Bispebjerg-Frederiksberg Hospital, Rigshospitalet, and Amager-Hvidovre Hospital). Screening, randomization, and protocol-specified assessments are performed at two sites (Herlev-Gentofte Hospital and Odense University Hospital). All assessments are performed at both sites, except RHC, which is only performed in patients randomized at Odense University Hospital and DXA-scan, and 51Cr-EDTA clearance and dobutamine stress-echocardiography, which are only performed in patients randomized at Herlev-Gentofte Hospital (Fig.?2). The study protocol and the used methods are routine procedures at the performing sites [40, 41]. At present (December 2018), 112 patients have been randomized and enrolment follows the planned schedule. It is expected that the last patients last visit will be in October 2019. Steering committeeThe steering committee consists of JJ, MO, CK, MKP, CT, IG, LK (chair), FG, EF, NEB, LV, JEM, and MS. The steering committee is responsible for the design, monitoring, reporting, and publication of the trial. Primary investigators are MS at Herlev-Gentofte Hospital and JEM at Odense University Hospital. The steering committee will have access to the final trial dataset. Monitoring and data collectionData will be collected and stored using electronic case report forms (eCRFs) constructed in the Research Electronic Data Capture (REDCap) system (Vanderbilt University ?2018). Corresponding source documents are stored at the experimental sites in accordance with the rules and regulations of the Danish Data Protection Agency to ensure confidentiality. The study is monitored by the GCP units at the University of Copenhagen and the University of Southern Denmark based on a specific monitoring plan. The GCP units are independent from the steering committee. Ethics and adverse eventsThe safety of the randomized patients will be monitored continuously based on recording of AEs and severe adverse events (SAEs) from signing the informed consent form through four weeks after the end-of-study visit. The data will be collected and recorded.