The HALT Progression of Polycystic Kidney Disease (HALT-PKD) (HALT PKD)
Number of Subjects in Study Archive: 1044 (558 - Study A, 486 - Study B)
Study Design: Clinical Trial
Conditions: Kidney Diseases, Kidney Diseases, Cystic, Polycystic Kidney Diseases
Duration: January 2006 - August 2014
# Recruitment Centers: 7
Treatment: ACE-I/ARB combination therapy; ACE-I monotherapy; standard blood pressure control; low blood pressure control (study A only)
Available Genotype Data: No
Image Summary: No
Transplant Type: None
Does it have dialysis patients: No
Clinical Trials URL: http://www.clinicaltrials.gov/show/NCT01885559
Autosomal dominant polycystic kidney disease (ADPKD) impacts 1 in 400 to 1 in 1000 live births and accounts for about 4.6% of the kidney replacement population in the US. Hypertension is the most common manifestation and an important risk factor for its progression to end stage renal disease (ESRD) and cardiovascular morbidity and mortality.
The HALT Progression of Polycystic Kidney Disease (HALT-PKD) studies are two simultaneous multicenter clinical trials designed to test the efficacy of interruption of the renin-angiotestin-aldosterone system (RAAS) on the progression of cystic disease and the decline in renal function in ADPKD. Specifically, the studies test the effects of ACE-I/ARB combination therapy as compared to ACE-I monotherapy in hypertensive ADPKD subjects.
The two studies vary on eligibility criteria (particularly kidney function), blood pressure treatment, and primary outcome measure. Study A investigates treatment effects on individuals with early ADPKD and implements a standard (120-130/70-80 mm Hg) vs. low (95-110/60-75 mmHg) blood pressure control target for both treatment arms in a 2x2 design. Study B investigates treatment effects on individuals with moderately advanced ADPKD in the setting of standard blood pressure control (110-130/80 mm Hg). Participants enrolled in study A will be followed for at least five years, while those enrolled in study B will be followed for five to eight years, with the average length of follow-up being six and a half years.
The complete HALT-PKD data package is available for request.
The primary objective of the HALT-PKD study A is to investigate the efficacy of ACE-I/ARB combination therapy as compared to ACE-I monotherapy and usual vs. low blood pressure targets on the percent change in kidney volume in participants with preserved renal function.
The primary objective of the HALT-PKD study B is to investigate the efficacy ACE-I/ARB combination therapy as compared to ACE-I monotherapy in the setting of standard blood pressure control on the time to a 50% reduction of baseline eGFR, ESRD or death, in hypertensive individuals with moderate renal insufficiency.
The primary outcome measure of study A is the change in total kidney volume, as assessed by abdominal magnetic resonance imaging at baseline, two years, and four years follow-up. Kidney function measured by eGFR will serve as a secondary outcome measure.
The primary outcome measure of study B is time to 50% reduction of baseline eGFR, end stage renal disease (ESRD) defined as initiation of dialysis or preemptive transplant, or death.
Secondary outcome measures for both studies include examination of albuminuria, aldosterone, hospitalizations, pain, and quality of life in two components: physical and mental.
Study A enrolled individuals aged 15 to 49 diagnosed with ADPKD and a GFR of >60 mL/min/1.73 m2.
Study B enrolled individuals aged 18 to 64 diagnosed with ADPKD and a GFR in the range of 25-60 mL/min/1.73 m2. In addition, all participants had high-normal blood pressure or were hypertensive, as defined by having BP ≥ 130/80 or receiving treatment for hypertension.
Study A: In early ADPKD, the combination of lisinopril and telmisartan did not significantly alter the rate of increase in total kidney volume. As compared with standard bloodpressure control, rigorous blood-pressure control was associated with a slower increase in total kidney volume, no overall change in the estimated GFR, a greater decline in the left-ventricular-mass index, and greater reduction in urinary albumin excretion.
Study B: Monotherapy with an ACE inhibitor was associated with blood pressure control in most patients with ADPKD and stage 3 chronic kidney disease. The addition of an ARB did not alter the decline in the estimated GFR.