HALT Progression of Polycystic Kidney Disease (HALT PKD) Study B

Condition(s) targeted: Kidney, Polycystic

Intervention: Lisinopril (Drug); Telmisartan (Drug); Placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Official(s) and/or principal investigator(s):
Robert Schrier, M.D., Study Chair, Affiliation: University of Colorado, Denver
Arlene Chapman, M.D., Principal Investigator, Affiliation: Emory University
Ronald Perrone, M.D., Principal Investigator, Affiliation: Tufts University-New England Medical Center
Vicente Torres, M.D., Principal Investigator, Affiliation: Mayo Clinic
Marva Moxey-Mims, M.D., Study Director, Affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Charity G Moore, PhD, Principal Investigator, Affiliation: University of Pittsburgh

The efficacy of interruption of the renin-angiotensin-aldosterone system (RAAS) on the progression of cystic disease and on the decline in renal function in autosomal dominant kidney disease (ADPKD) will be assessed in two simultaneous multicenter randomized clinical trials targeting different levels of kidney function: 1) early disease defined by GFR >60 mL/min/1. 73 m2 (Study A); and 2) moderately advanced disease defined by GFR 25-60 mL/min/1. 73 m2 (Study B). Participants will be recruited and enrolled, either to Study A or B, over the first three years. Participants 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. Combination therapy will use angiotensin-converting-enzyme inhibitor (ACE-I) and an angiotensin-receptor blocker (ARB). Monotherapy will use ACE-I alone.

Official title: Polycystic Kidney Disease-Treatment Network

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Number of Participants With 50% Reduction of Baseline eGFR, End Stage Renal Disease (ESRD, Initiation of Dialysis or Preemptive Transplant), or Death.

Secondary outcome:

Albuminuria

Aldosterone

Hospitalizations

Cardiovascular Hospitalizations

Quality of Life Physical Component Summary

Quality of Life Mental Component Summary

Pain

Detailed description: * Specific Aim of Study B To study the effects of ACE-I/ARB combination therapy as compared to ACE-I monotherapy in the setting of standard blood pressure control (110-130/80 mm Hg) on the time to a 50% reduction of baseline estimated Glomerular Filtration Rate (eGFR), end-state renal disease (ESRD) or death, in hypertensive individuals with moderate renal insufficiency (GFR 25-60 mL/min/1. 73m2). * Hypothesis to be tested in Study B In hypertensive ADPKD individuals with moderate renal insufficiency (GFR 25-60 mL/min/1. 73 m2), intensive blockade of the RAAS using combination ACE-I/ARB therapy will slow the decline in kidney function over ACE-I monotherapy, independent of standard blood pressure control (110-130/80 mm Hg).

Minimum age: 15 Years. Maximum age: 64 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnosis of ADPKD.

- Age 15-49 (Study A); Age 18-64 (Study B).

- GFR >60 mL/min/1. 73 m2 (Study A); GFR 25-60 mL/min/1. 73 m2 (Study B).

- BP ≥130/80 or receiving treatment for hypertension.

- Informed Consent.

Exclusion Criteria:

- Pregnant/intention to become pregnant in 4-6 yrs.

- Documented renal vascular disease.

- Spot urine albumin-to-creatinine ratio of >0. 5 (Study A) or ≥1. 0 (Study B) and/or

findings suggestive of kidney disease other than ADPKD.

- Diabetes requiring insulin or oral hypoglycemic agents / fasting serum glucose of

>126 mg/dl / random non-fasting glucose of >200 mg/dl.

- Serum potassium >5. 5 milliequivalent (mEq) /L for participants currently on ACE-I or

ARB; >5. 0 mEq/L for participants not currently on ACE-I or ARB.

- History of angioneurotic edema or other absolute contraindication for ACE-I or ARB.

Intolerable cough associated with ACE-I is defined as a cough developing within six months of initiation of ACE-I in the absence of other causes and resolving upon discontinuation of the ACE-I.

- Indication (other than hypertension) for β-blocker or calcium channel blocker therapy

(e. g. angina, past myocardial infarction, arrhythmia), unless approved by the site principal investigator. (PI may choose to accept an individual who is on only a small dose of one of these agents and would otherwise be eligible.)

- Systemic illness necessitating nonsteroidal antiinflammatory drugs (NSAIDs),

immunosuppressant or immunomodulatory medications.

- Systemic illness with renal involvement.

- Hospitalized for acute illness in past 2 months.

- Life expectancy <2 years.

- History of non-compliance.

- Unclipped cerebral aneurysm >7mm diameter.

- Creatine supplements within 3 months of screening visit.

- Congenital absence of a kidney (also total nephrectomy for Study B).

- Known allergy to sorbitol or sodium polystyrene sulfonate.

- Exclusions specific to magnetic resonance (MR) imaging (Study A).

University of Colorado Health Sciences Center, Denver (Aurora), Colorado 800045, United States

Emory University School of Medicine, Atlanta, Georgia 30322, United States

University of Kansas Medical Center, Kansas City, Kansas 66160, United States

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States

Tufts University-New England Medical Center, Boston, Massachusetts 02111, United States

Mayo Clinic, Rochester, Minnesota 55905, United States

Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States

Polycystic Kidney Disease Foundation Website

Starting date: January 2006
Last updated: February 25, 2015