HALT Progression of Polycystic Kidney Disease Study B
Condition: Kidney, Polycystic
MeSH terms: Kidney Diseases; Polycystic Kidney Diseases
Intervention: Lisinopril; Telmisartan; Placebo
Intervention description: Lisinopril titrated to 5mg, 10mg, 20mg, 40mg as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.; Telmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.; Placebo titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.
Intervention MeSH terms: Telmisartan; Lisinopril; Angiotensin-Converting Enzyme Inhibitors
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 486.0
Sex: All
Minimum age: 15 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: polycystic kidney disease; polycystic; kidney; disease; adpkd; halt; pkd; blood pressure; bp; hypertension; renal; renin-angiotensin-aldosterone-system; RAAS

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.

      Combination therapy will use angiotensin-converting-enzyme inhibitor (ACE-I) and an
      angiotensin-receptor blocker (ARB). Monotherapy will use ACE-I alone.
    

Eligibility 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).