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Publisher Copyright: 2016 European Society of Cardiology", TOPCAT was funded by the National Institutes of Health, NHLBI, Bethesda, MD, contract N01 HC45207. This work is solely the responsibility of the authors and does not necessarily represent the official views of the NHLBI or National Institutes of Health. TOPCAT was supported by the National Heart, Lung, and Blood Institute (NHLBI) contract HHSN268200425207C awarded to New England Research Institutes Clinical Trials Coordinating Center. Special thanks go to Yves Rosenberg, MD who served as NHLBI's Executive Secretary of the DSMB. The authors thank Ms Rachel Rosenberg for her assistance in manuscript processing and submission. Note = "Funding Information: TOPCAT was supported by the National Heart, Lung, and Blood Institute (NHLBI) contract HHSN268200425207C awarded to New England Research Institutes Clinical Trials Coordinating Center.
#Topcat spironolactone trial
In TOPCAT, spironolactone-associated renal dysfunction emerged as a potentially trial-threatening adverse event and, although clinically important, did not lead to compromise of patient safety, trial interruption, termination, or apparent loss of treatment effectiveness.", In clinical trials, DSMBs and co-ordinating centres should have the resources to detect, investigate, and adjudicate unexpected safety issues, with goals of ensuring patient safety and preserving the potential for detection of therapeutic effectiveness. Although no discrete mechanism for the spironolactone-associated renal adverse event signal was identified, likely possibilities are discussed. The trial continued uninterrupted throughout the review, which reached the conclusions that spironolactone-associated renal dysfunction did not compromise overall patient safety or interfere with a perceived efficacy signal. The detection of a greater than expected incidence of deterioration in renal function, occurring in 6.1% of patients in the spironolactone arm compared with 3.9% in the placebo arm (P = 0.009), led to an in-depth DSMB review of associated study medication withdrawals and adverse events.
![topcat spironolactone topcat spironolactone](https://www.ahajournals.org/cms/asset/ee723c25-9e17-4d89-9603-243a0a3b3888/34fig01.jpeg)
We describe how the TOPCAT DSMB detected, investigated, and adjudicated an unexpectedly large renal adverse event signal midway through the trial, and offer general guidelines for dealing with similar unanticipated occurrences in future trials. The role of DSMBs is expanding, and ideally should include post-hoc reporting of deliberative processes related to clinically important safety issues or factors that could impact on future trial designs. In TOPCAT, spironolactone-associated renal dysfunction emerged as a potentially trial-threatening adverse event and, although clinically important, did not lead to compromise of patient safety, trial interruption, termination, or apparent loss of treatment effectiveness.Ībstract = "Clinical trial Data and Safety Monitoring Boards (DSMBs) have a primary obligation of ensuring study participant safety, while maintaining trial integrity.
![topcat spironolactone topcat spironolactone](https://onlinelibrary.wiley.com/cms/asset/f9c4aae3-8a02-4020-a416-15d567b84bbf/ejhf1979-fig-0001-m.jpg)
Clinical trial Data and Safety Monitoring Boards (DSMBs) have a primary obligation of ensuring study participant safety, while maintaining trial integrity.