Overview

This trial is active, not recruiting.

Condition kidney, polycystic
Treatments lisinopril and placebo, lisinopril and telmisartan
Phase phase 3
Sponsor National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator Boehringer Ingelheim
Start date January 2006
End date June 2014
Trial size 486 participants
Trial identifier NCT01885559, DK62401-PKD-TN (IND)

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Placebo Comparator)
ACE-I + placebo and standard blood pressure control of 110-130/80 mm Hg
lisinopril and placebo ACE-I
Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and placebo titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.
(Active Comparator)
ACE-I + ARB and standard blood pressure control of 110-130/80 mm Hg
lisinopril and telmisartan ACE-I
Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and telmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.

Primary Outcomes

Measure
Time to 50% reduction of baseline eGFR, ESRD (initiation of dialysis or preemptive transplant), or death.
time frame: Patients followed for 5-8 years with average of 6.5 years follow up

Secondary Outcomes

Measure
Albuminuria
time frame: up to 8 years (annually assessed)
Aldosterone
time frame: up at 8 years (annually assessed)
Hospitalizations
time frame: up to 8 years
Cardiovascular Hospitalizations
time frame: up to 8 years
Quality of Life Physical Component
time frame: up to 8 years (annually assessed)
Quality of Life Mental Component Summary
time frame: up to 8 years (annually assessed)
Pain
time frame: up to 8 years (annually assessed)

Eligibility Criteria

Male or female participants from 15 years up to 64 years old.

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 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 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 MR imaging (Study A).

Additional Information

Official title Polycystic Kidney Disease-Treatment Network
Principal investigator Arlene Chapman, M.D.
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 eGFR, 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).
Trial information was received from ClinicalTrials.gov and was last updated in June 2013.
Information provided to ClinicalTrials.gov by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).