HALT Progression of Polycystic Kidney Disease Study A

Overview

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 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; NCT01885559). Participants will be recruited and enrolled, either to Study A or B, over the first three years. Participants enrolled in Study A will be followed for at least 5 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 two concurrent randomized clinical trials differ by eligibility criteria, interventions and outcomes to be studied.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Factorial Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: June 2014

Detailed Description

* Specific Aims of Study A To study the efficacy of angiotensin-converting-enzyme inhibitor (ACE-I) and angiotensin-receptor blockade (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 (GFR >60 mL/min/1.73m2)and high-normal blood pressure or hypertension (>130/80 mm Hg). * Hypotheses to be tested in Study A In ADPKD individuals with hypertension or high-normal blood pressure and relatively preserved renal function (GFR >60 mL/min/1.73 m2), multi-level blockade of the RAAS using ACE-I/ARB combination therapy will delay progression of cystic disease as compared to ACE-I monotherapy, and a low blood pressure goal will delay progression as compared with standard control.

Interventions

  • Drug: Lisinopril
    • Lisinopril titrated to 5mg, 10mg, 20mg, 40mg
  • Drug: Telmisartan
    • Telmisartan/Placebo titrated to 40mg and 80mg, as tolerated by participants
  • Drug: Placebo
    • Telmisartan/Placebo titrated to 40mg and 80mg, as tolerated by participants
  • Other: Standard Blood Pressure Control
    • Achieve standard blood pressure control of 120-130/70-80 mm Hg using step dosing specified in protocol of lisinopril, study drug, hydrochlorothiazide, metoprolol, or non-dihydropyridine and dihydropyridine calcium channel blockers (diltiazem), clonidine, minoxidil, hydralazine at the discretion of the investigator
  • Other: Low Blood Pressure Control
    • Achieve low blood pressure control of 95-110/60-75 mm Hg using step dosing specified in protocol of lisinopril, study drug, hydrochlorothiazide, metoprolol, or non-dihydropyridine and dihydropyridine calcium channel blockers (diltiazem), clonidine, minoxidil, hydralazine at the discretion of the investigator

Arms, Groups and Cohorts

  • Active Comparator: Study A, Arm 1
    • Lisinopril + Telmisartan (ACE-I + ARB) and standard blood pressure control of 120-130/70-80 mm Hg
  • Active Comparator: Study A, Arm 2
    • Lisinopril + Telmisartan (ACE-I + ARB) and low blood pressure control of 95-110/60-75 mm Hg
  • Placebo Comparator: Study A, Arm 3
    • Lisinopril + Placebo (ACE-I + Placebo) and standard blood pressure control of 120-130/70-80 mm Hg
  • Placebo Comparator: Study A, Arm 4
    • Lisinopril + Placebo (ACE-I + Placebo) and low blood pressure control of 95-110/60-75 mm Hg

Clinical Trial Outcome Measures

Primary Measures

  • Study A: Percent Annual Change in Total Kidney Volume
    • Time Frame: Baseline and 2-, 4- and 5-year follow-up
    • Annual percentage change in total kidney volume as assessed by abdominal magnetic resonance imaging (MRI) at baseline, 2 years, 4 years, and 5 years follow-up.

Secondary Measures

  • Kidney Function (eGFR)
    • Time Frame: Up to 96 months (6 month assessments)
    • The estimated GFR was calculated by means of the Chronic Kidney Disease Epidemiology Collaboration equation with the use of central serum creatinine measurements.
  • Albuminuria
    • Time Frame: Up to 96 months (assessed annually)
    • Urine albumin excretion, centrally processed from 24 hour urine collection
  • Aldosterone
    • Time Frame: Up to 96 months (assessed annually)
    • Urinary aldosterone excretion, centrally processed, 24 hour urine collection
  • Left Ventricular Mass Index
    • Time Frame: 0, 24 months, 48 months, 60 months
    • Left ventricular mass index (g/m^2) measured by MRI, centrally reviewed and measured
  • Renal Blood Flow
    • Time Frame: 0, 24 months, 48 months, 60 months
    • renal blood flow (mL/min/1.73 m^2) from MRI, centrally reviewed and measured. This outcome was more difficult to measure resulting in more missing data than other MRI outcomes such as total kidney volume (TKV) and left ventricular mass index (LVMI).
  • All-Cause Hospitalizations
    • Time Frame: Up to 96 months
  • Quality of Life Physical Component Summary
    • Time Frame: baseline, 12, 24, 36, 48, 60, 72, 84, and 96 months (assessed annually)
    • Short Form-36 Quality of Life Physical Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome)
  • Quality of Life Mental Component Summary
    • Time Frame: baseline, 12, 24, 36, 48, 60, 72, 84, and 96 months (assessed annually)
    • Short Form-36 Quality of LIfe Mental Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome)

Participating in This Clinical Trial

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 per liter (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 imaging (Study A).

Gender Eligibility: All

Minimum Age: 15 Years

Maximum Age: 64 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Collaborator
    • Boehringer Ingelheim
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Robert Schrier, M.D., Study Chair, University of Colorado, Denver
    • Arlene Chapman, M.D., Principal Investigator, Emory University
    • Ronald Perrone, M.D., Principal Investigator, Tufts University-New England Medical Center
    • Vicente Torres, M.D., Principal Investigator, Mayo Clinic
    • Marva Moxey-Mims, M.D., Study Director, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
    • Charity G Moore, MS,PhD, Principal Investigator, University of Pittsburgh

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.