HALT Progression of Polycystic Kidney Disease Study B

NCT01885559 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: HALT PKD BU01DK062401U01DK082230
• Study Type: interventional
• Target: 486
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Kidney, Polycystic

Keywords

polycystic kidney disease; polycystic; kidney; disease; adpkd; halt; pkd; blood pressure; bp; hypertension; renal; renin-angiotensin-aldosterone-system; RAAS

Outcome Measures

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.

  Patients followed for 5-8 years with average of 6.5 years follow up

Secondary Outcomes (7)

• Albuminuria

  up to 8 years (annually assessed)

• Aldosterone

  up at 8 years (annually assessed)

• Hospitalizations

  up to 8 years

• Cardiovascular Hospitalizations

  up to 8 years

• Quality of Life Physical Component Summary

  up to 8 years (annually assessed)

Study Arms (2)

ACE-I + placebo

PLACEBO COMPARATOR

Monotherapy of lisinopril and placebo. Standard blood pressure control of 110-130/80 mm Hg

Drug: Lisinopril; Drug: Placebo

ACE-I + ARB

ACTIVE COMPARATOR

Dual therapy of lisinopril and telmisartan treatments. Standard blood pressure control of 110-130/80 mm Hg.

Drug: Lisinopril; Drug: Telmisartan

Interventions

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.

Also known as: ACE-I, ACE, Ace-Inhibitor

ACE-I + ARB; ACE-I + placebo

Telmisartan DRUG

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

Also known as: ARB

ACE-I + 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.

Also known as: Control

ACE-I + placebo

Eligibility Criteria

• Age: 15 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• Boehringer Ingelheim: collaborator
• Merck Sharp & Dohme LLC: collaborator
• Polycystic Kidney Disease Foundation: collaborator
• University of Pittsburgh: collaborator
• Washington University School of Medicine: collaborator

Study Sites (7)

University of Colorado Health Sciences Center

Aurora, Colorado, 800045, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Tufts University-New England Medical Center

Boston, Massachusetts, 02111, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Related Publications (3)

• St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

  PMID: 39356039 DERIVED

• Chebib FT, Zhou X, Garbinsky D, Davenport E, Nunna S, Oberdhan D, Fernandes A. Tolvaptan and Kidney Function Decline in Older Individuals With Autosomal Dominant Polycystic Kidney Disease: A Pooled Analysis of Randomized Clinical Trials and Observational Studies. Kidney Med. 2023 Apr 14;5(6):100639. doi: 10.1016/j.xkme.2023.100639. eCollection 2023 Jun.

  PMID: 37250503 DERIVED

• Torres VE, Abebe KZ, Chapman AB, Schrier RW, Braun WE, Steinman TI, Winklhofer FT, Brosnahan G, Czarnecki PG, Hogan MC, Miskulin DC, Rahbari-Oskoui FF, Grantham JJ, Harris PC, Flessner MF, Moore CG, Perrone RD; HALT-PKD Trial Investigators. Angiotensin blockade in late autosomal dominant polycystic kidney disease. N Engl J Med. 2014 Dec 11;371(24):2267-76. doi: 10.1056/NEJMoa1402686. Epub 2014 Nov 15.

  PMID: 25399731 DERIVED

Related Links

• Polycystic Kidney Disease Foundation Website

MeSH Terms

Conditions

Polycystic Kidney Diseases; Disease; Polycystic Kidney, Autosomal Dominant; Familial paroxysmal dystonia; Hypertension

Interventions

Lisinopril; Angiotensin-Converting Enzyme Inhibitors; Telmisartan

Condition Hierarchy (Ancestors)

Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Vicente Torres
• Organization: Mayo Clinic

torres.vicente@mayo.edu

Study Officials

• Robert Schrier, M.D.

  University of Colorado, Denver

  STUDY CHAIR

• Arlene Chapman, M.D.

  Emory University

  PRINCIPAL INVESTIGATOR

• Ronald Perrone, M.D.

  Tufts University-New England Medical Center

  PRINCIPAL INVESTIGATOR

• Vicente Torres, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Marva Moxey-Mims, M.D.

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

  STUDY DIRECTOR

• Charity G Moore, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2013
• First Posted: June 25, 2013
• Study Start: January 1, 2006
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: April 22, 2020
• Results First Posted: March 10, 2015

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share

Locations

US (7)