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Phase 3 N=486 Randomized Quadruple-blind Treatment

HALT Progression of Polycystic Kidney Disease Study B

Kidney, Polycystic

Enrolled (actual)
486
Serious AEs
36.2%
Results posted
Mar 2015
Primary outcome: Primary: Number of Participants With 50% Reduction of Baseline eGFR, End Stage Renal Disease (ESRD, Initiation of Dialysis or Preemptive Transplant), or Death. — 116; 115 participants — p=0.58

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Lisinopril (Drug); Telmisartan (Drug); Placebo (Drug)
Age
Pediatric, Adult · 15+ yrs
Sex
All
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Primary completion
Jun 2014

Outcome Measures

OutcomeResultp-value
PRIMARY
Number of Participants With 50% Reduction of Baseline eGFR, End Stage Renal Disease (ESRD, Initiation of Dialysis or Preemptive Transplant), or Death.
116; 115 0.58
SECONDARY
Albuminuria
7.5; 7.3 0.88
SECONDARY
Aldosterone
-8.8; -10.2 0.17
SECONDARY
Hospitalizations
173; 136 0.85
SECONDARY
Cardiovascular Hospitalizations
29; 16 0.57
SECONDARY
Quality of Life Physical Component Summary
-0.64; -0.68 0.75
SECONDARY
Quality of Life Mental Component Summary
-0.031; -0.079 0.66
SECONDARY
Back or Flank Pain
43; 46 0.64

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 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).
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01885559). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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