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

National Institutes of Health (NIH)

Status and phase: Completed; Phase 3

Conditions: Kidney, Polycystic

Treatments: Drug: Telmisartan; Drug: Placebo; Drug: Lisinopril; Other: Standard Blood Pressure Control; Other: Low Blood Pressure Control

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00283686

U01DK062401 (U.S. NIH Grant/Contract)

HALT PKD A

U01DK082230 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 558 patients

Sex: All

Ages: 15 to 64 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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558 participants in 4 patient groups, including a placebo group

Study A, Arm 1

Active Comparator group

Description:

Lisinopril + Telmisartan (ACE-I + ARB) and standard blood pressure control of 120-130/70-80 mm Hg

Treatment:

Other: Standard Blood Pressure Control

Drug: Lisinopril

Drug: Telmisartan

Study A, Arm 2

Active Comparator group

Description:

Lisinopril + Telmisartan (ACE-I + ARB) and low blood pressure control of 95-110/60-75 mm Hg

Treatment:

Other: Low Blood Pressure Control

Drug: Lisinopril

Drug: Telmisartan

Study A, Arm 3

Placebo Comparator group

Description:

Lisinopril + Placebo (ACE-I + Placebo) and standard blood pressure control of 120-130/70-80 mm Hg

Treatment:

Other: Standard Blood Pressure Control

Drug: Placebo

Drug: Lisinopril

Study A, Arm 4

Placebo Comparator group

Description:

Lisinopril + Placebo (ACE-I + Placebo) and low blood pressure control of 95-110/60-75 mm Hg

Treatment:

Other: Low Blood Pressure Control

Drug: Placebo

Drug: Lisinopril