Closeout of the HALT-PKD trials

• Type of Material: Article
• Authors: Charity G. Moore, Carolinas HealthCare System; Susan Spillane, University of Pittsburgh; Gertrude Simon, Tufts Medical Center; Barbara Maxwell, Beth Israel Deaconess Medical Center; Frederic Rahbari Oskoui, Emory University; William E. Braun, Cleveland Clinic; Arlene Chapman, Emory University; Robert W. Schrier, University of Colorado; Vicente E. Torres, Mayo Clinic; Ronald D. Perrone, Tufts Medical Center; Theodore I. Steinman, Beth Israel Deaconess Medical Center; Godela Brosnahan, University of Colorado; Peter G. Czarnecki, Beth Israel Deaconess Medical Center; Peter C. Harris, Mayo Clinic; Dana C. Miskulin, Tufts Medical Center; Michael F. Flessner, National Institutes of Health; K. Ty Bae, University of Pittsburgh; Kaleab Z. Abebe, University of Pittsburgh; Marie C. Hogan, Mayo Clinic
• Language: English
• Date: 2015-09-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cct.2015.07.017
• Title of Journal or Parent Work: Contemporary Clinical Trials
• Volume: 44
• Start Page: 48
• End Page: 55
• Grant/Funding Information: This study was supported by cooperative agreements (grants U01DK62408 Emory University, U01DK62401 Washington University in St. Louis, U01DK62410 Mayo Clinic, U01DK62402 University of Colorado, U01DK62411 Tufts Medical Center, and U01DK082230 University of Pittsburgh) with the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, the National Center for Research Resources General Clinical Research Centers (RR000039 Emory University, RR000585 Mayo Clinic, RR000054 Tufts Medical Center, RR000051 University of Colorado, RR023940 University of Kansas Medical Center, and RR001032 Beth Israel Deaconess Medical Center), and the Clinical and Translational Science Awards at the participating institutions (RR025008 and UL1TR000454 Emory University, RR024150 and UL1TR00135 Mayo Clinic, RR025752 and UL1TR001064 Tufts University, RR025780 and UL1TR001082 University of Colorado, RR025758 and UL1TR001102 Beth Israel Deaconess Medical Center, RR033179 and UL1TR000001 University of Kansas Medical Center and RR024989 and UL1TR000439 Cleveland Clinic).
• Keywords: Research & Experimental Medicine; Science & Technology; Patient safety; Regulatory; Pharmacology & Pharmacy; Data coordination; Life Sciences & Biomedicine; Medicine, Research & Experimental; Closeout; Unblinding
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Health Care Management

Abstract

Background: The HALT Polycystic Kidney Disease Trials Network consisted of two randomized, double blind, placebo-controlled trials among patients with autosomal dominant polycystic kidney disease. The trials involved 5–8 years of participant follow-up with interventions in blood pressure and antihypertensive therapy. We provide a framework for designing and implementing closeout near the end of a trial while ensuring patient safety and maintaining scientific rigor and study morale. Methods: We discuss issues and resolutions for determining the last visit, tapering medications, and unblinding of participants to study allocation and results. We also discuss closure of clinical sites and Data Coordinating Center responsibilities to ensure timely release of study results and meeting the requirements of regulatory and funding authorities. Results: Just over 90% of full participants had a 6-month study visit prior to their last visit preparing them for trial closeout. Nearly all patients wanted notification of study results (99%) and treatment allocation (99%). All participants were safely tapered off study and open label blood pressure medications. Within 6 months, the trials were closed, primary papers published, and 805 letters distributed to participants with results and allocation. DCC obligations for data repository and clinicaltrials.gov reporting were completed within 12 months of the last study visit. Conclusions: Closeout of our trials involved years of planning and significant human and financial resources. We provide questions for investigators to consider when planning closeout of their trials with focus on (1) patient safety (2) dissemination of study results and (3) compliance with regulatory and funding responsibilities.