The HALT-Polycystic Kidney Disease (PKD) trials comprise 2 fully enrolled randomized controlled trials (A &B) conducted at 7 clinical sites supported by a central imaging facility, a drug distribution center, and 2 central laboratories. HALT-PKD Study A uses a 2x2 factorial design to evaluate the impact of rennin-angiotensin-aldosterone system (RAAS) blockade and 2 levels of blood pressure control on structural progression of disease in 558 high-normal or hypertensive PKD patients with estimated glomerular filtration rate (GFR) >60 ml/min/1.73m2. The primary outcome is total kidney volume (TKV) measured at 0, 24, and 48 months. HALT- PKD Study B evaluates the impact of RAAS blockade on progression of disease in 486 hypertensive PKD patients with estimated GFR 30-60 ml/min/1.73m2. The primary outcome is a combined endpoint defined by >50 percent reduction in eGFR, ESRD, or death. Participants are followed for 4-7 years. For Study A, there is strong evidence to show the impact of TKV on kidney function (GFR) takes several years to manifest implying the short period of follow-up for Study A (48 months) may be insufficient to see changes on kidney function. For Study B, the observed number of endpoints at 5 years is lower than had been predicted to provide power for 25 percent reduction in outcome. As a result of these new findings and interim analyses, the DSMB approved extension of both studies through July 2014 to allow an additional measure for Study A (60 months) and 5-8 years follow-up for study B. We propose to continue to serve as the HALT-PKD DCC by 1) collaborating with study investigators, managing protocol and regulatory compliance, facilitating the transfer of data, images, and bio-specimens, and supporting HALT- PKD activities for quality control, endpoint adjudication, and blood pressure management;2) maintaining the Web-based data management system that incorporates data tracking, entry, quality control, and report generation;3) conducting interim and final statistical analyses to support the study aims including the future primary analyses for Study A and Study B. Public

Public Health Relevance

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder leading to end stage renal disease. Demonstration that rigorous treatment with a combination of ACE-I and ARB will attenuate renal disease progression will provide a cost-effective, readily available, clinically practical intervention for individuals with ADPKD.

Agency
National Institute of Health (NIH)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK082230-07
Application #
8658816
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Flessner, Michael Francis
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Torres, Vicente E; Abebe, Kaleab Z; Chapman, Arlene B et al. (2014) Angiotensin blockade in late autosomal dominant polycystic kidney disease. N Engl J Med 371:2267-76
Schrier, Robert W; Abebe, Kaleab Z; Perrone, Ronald D et al. (2014) Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med 371:2255-66