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Completed

NCT Number: NCT01885559

HALT Progression of Polycystic Kidney Disease Study B

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.

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Key information

Conditions

Kidney, Polycystic Abnormalities, Multiple Cardiovascular Diseases Ciliopathies Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Disease Familial paroxysmal dystonia Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Hypertension Kidney Diseases Kidney Diseases, Cystic Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Polycystic Kidney Diseases Polycystic Kidney, Autosomal Dominant Urogenital Diseases Urologic Diseases Vascular Diseases

Age range

15 year–64 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University of Colorado Health Sciences Center, Aurora, Colorado, United States

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About this study

  • 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 estimated Glomerular Filtration Rate (eGFR), end-state renal disease (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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Lisinopril

Drug

Lisinopril titrated to 5mg, 10mg, 20mg, 40mg as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.

Other names: ACE-I, ACE, Ace-Inhibitor

Telmisartan

Drug

Telmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.

Other names: ARB

Placebo

Drug

Placebo titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.

Other names: Control

Primary outcomes

  1. Number of Participants With 50% Reduction of Baseline eGFR, End Stage Renal Disease (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

  1. Albuminuria

    Time frame: up to 8 years (annually assessed)

    Annual percent change in 24 hour urine albumin, centrally processed. Data from multiple years were analyzed with the primary focus on the change over time for the measure (from the slope of the model). The measure presented is the average annual percent change across the 8 years.

  2. Aldosterone

    Time frame: up at 8 years (annually assessed)

    Annual percent change in urinary aldosterone, centrally processed measure. Data from multiple years were analyzed with the primary focus on the change over time for the measure (from the slope for time from the model). The measure presented is the average annual percent change across the 8 years.

  3. Hospitalizations

    Time frame: up to 8 years

    Hospitalization for any cause

  4. Cardiovascular Hospitalizations

    Time frame: up to 8 years

    Cause-specific hospitalizations (cardiovascular)

  5. Quality of Life Physical Component Summary

    Time frame: up to 8 years (annually assessed)

    Short Form-36 Quality of Life Physical Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome). Data from multiple years were analyzed with the primary focus on the change over time for the measure (from the slope for time from the model). The measure presented is the average annual change across the 8 years.

  6. Quality of Life Mental Component Summary

    Time frame: up to 8 years (annually assessed)

    Short Form-36 Quality of Life Mental Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome). Data from multiple years were analyzed with the primary focus on the change over time for the measure (from the slope for time from the model). The measure presented is the average annual change across the 8 years.

  7. Back or Flank Pain

    Time frame: 48 months

    Report of back or flank pain since the last visit (yes or no)

Sponsors and collaborators

Lead sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Nih

Collaborators

  • Boehringer Ingelheim
  • Merck Sharp & Dohme LLC
  • Polycystic Kidney Disease Foundation
  • University of Pittsburgh
  • Washington University School of Medicine

Registry information

Acronym: HALT PKD B

Important dates

Study start
2006
Primary completion
2014
Study completion
2014
First posted
Jun 25, 2013
Registry last updated
Apr 22, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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