HALT Progression of Polycystic Kidney Disease Study A

NCT00283686 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: HALT PKD AU01DK062401U01DK082230
• Study Type: interventional
• Target: 558
• 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 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; NCT01885559). Participants will be recruited and enrolled, either to Study A or B, over the first three years. Participants enrolled in Study A will be followed for at least 5 years, while those 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. The two concurrent randomized clinical trials differ by eligibility criteria, interventions and outcomes to be studied.

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)

• Study A: Percent Annual Change in Total Kidney Volume

  Annual percentage change in total kidney volume as assessed by abdominal magnetic resonance imaging (MRI) at baseline, 2 years, 4 years, and 5 years follow-up.

  Baseline and 2-, 4- and 5-year follow-up

Secondary Outcomes (8)

• Kidney Function (eGFR)

  Up to 96 months (6 month assessments)

• Albuminuria

  Up to 96 months (assessed annually)

• Aldosterone

  Up to 96 months (assessed annually)

• Left Ventricular Mass Index

  0, 24 months, 48 months, 60 months

• Renal Blood Flow

  0, 24 months, 48 months, 60 months

Study Arms (4)

Study A, Arm 1

ACTIVE COMPARATOR

Lisinopril + Telmisartan (ACE-I + ARB) and standard blood pressure control of 120-130/70-80 mm Hg

Drug: Lisinopril; Drug: Telmisartan; Other: Standard Blood Pressure Control

Study A, Arm 2

ACTIVE COMPARATOR

Lisinopril + Telmisartan (ACE-I + ARB) and low blood pressure control of 95-110/60-75 mm Hg

Drug: Lisinopril; Drug: Telmisartan; Other: Low Blood Pressure Control

Study A, Arm 3

PLACEBO COMPARATOR

Lisinopril + Placebo (ACE-I + Placebo) and standard blood pressure control of 120-130/70-80 mm Hg

Drug: Lisinopril; Drug: Placebo; Other: Standard Blood Pressure Control

Study A, Arm 4

PLACEBO COMPARATOR

Lisinopril + Placebo (ACE-I + Placebo) and low blood pressure control of 95-110/60-75 mm Hg

Drug: Lisinopril; Drug: Placebo; Other: Low Blood Pressure Control

Interventions

Lisinopril DRUG

Lisinopril titrated to 5mg, 10mg, 20mg, 40mg

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

Study A, Arm 1; Study A, Arm 2; Study A, Arm 3; Study A, Arm 4

Telmisartan DRUG

Telmisartan/Placebo titrated to 40mg and 80mg, as tolerated by participants

Also known as: ARB

Study A, Arm 1; Study A, Arm 2

Placebo DRUG

Telmisartan/Placebo titrated to 40mg and 80mg, as tolerated by participants

Study A, Arm 3; Study A, Arm 4

Standard Blood Pressure Control OTHER

Achieve standard blood pressure control of 120-130/70-80 mm Hg using step dosing specified in protocol of lisinopril, study drug, hydrochlorothiazide, metoprolol, or non-dihydropyridine and dihydropyridine calcium channel blockers (diltiazem), clonidine, minoxidil, hydralazine at the discretion of the investigator

Also known as: blood pressure control

Study A, Arm 1; Study A, Arm 3

Low Blood Pressure Control OTHER

Achieve low blood pressure control of 95-110/60-75 mm Hg using step dosing specified in protocol of lisinopril, study drug, hydrochlorothiazide, metoprolol, or non-dihydropyridine and dihydropyridine calcium channel blockers (diltiazem), clonidine, minoxidil, hydralazine at the discretion of the investigator

Also known as: blood pressure control

Study A, Arm 2; Study A, Arm 4

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 per liter (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 (6)

• 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

• Heerspink HJL, Inker LA, Tighiouart H, Collier WH, Haaland B, Luo J, Appel GB, Chan TM, Estacio RO, Fervenza F, Floege J, Imai E, Jafar TH, Lewis JB, Kam-Tao Li P, Locatelli F, Maes BD, Perna A, Perrone RD, Praga M, Schena FP, Wanner C, Xie D, Greene T; on behalf of CKD-EPI CT. Change in Albuminuria and GFR Slope as Joint Surrogate End Points for Kidney Failure: Implications for Phase 2 Clinical Trials in CKD. J Am Soc Nephrol. 2023 Jun 1;34(6):955-968. doi: 10.1681/ASN.0000000000000117. Epub 2023 Mar 15.

  PMID: 36918388 DERIVED

• Kim K, Trott JF, Gao G, Chapman A, Weiss RH. Plasma metabolites and lipids associate with kidney function and kidney volume in hypertensive ADPKD patients early in the disease course. BMC Nephrol. 2019 Feb 25;20(1):66. doi: 10.1186/s12882-019-1249-6.

  PMID: 30803434 DERIVED

• Schrier RW, Abebe KZ, Perrone RD, Torres VE, Braun WE, Steinman TI, Winklhofer FT, Brosnahan G, Czarnecki PG, Hogan MC, Miskulin DC, Rahbari-Oskoui FF, Grantham JJ, Harris PC, Flessner MF, Bae KT, Moore CG, Chapman AB; HALT-PKD Trial Investigators. Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med. 2014 Dec 11;371(24):2255-66. doi: 10.1056/NEJMoa1402685. Epub 2014 Nov 15.

  PMID: 25399733 DERIVED

• Hogan MC, Abebe K, Torres VE, Chapman AB, Bae KT, Tao C, Sun H, Perrone RD, Steinman TI, Braun W, Winklhofer FT, Miskulin DC, Rahbari-Oskoui F, Brosnahan G, Masoumi A, Karpov IO, Spillane S, Flessner M, Moore CG, Schrier RW. Liver involvement in early autosomal-dominant polycystic kidney disease. Clin Gastroenterol Hepatol. 2015 Jan;13(1):155-64.e6. doi: 10.1016/j.cgh.2014.07.051. Epub 2014 Aug 9.

  PMID: 25111236 DERIVED

• Torres VE, Chapman AB, Perrone RD, Bae KT, Abebe KZ, Bost JE, Miskulin DC, Steinman TI, Braun WE, Winklhofer FT, Hogan MC, Oskoui FR, Kelleher C, Masoumi A, Glockner J, Halin NJ, Martin DR, Remer E, Patel N, Pedrosa I, Wetzel LH, Thompson PA, Miller JP, Meyers CM, Schrier RW; HALT PKD Study Group. Analysis of baseline parameters in the HALT polycystic kidney disease trials. Kidney Int. 2012 Mar;81(6):577-85. doi: 10.1038/ki.2011.411. Epub 2011 Dec 28.

  PMID: 22205355 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. Arlene Chapman
• Organization: Emory University

abchapm@emory.edu

(404) 712-1993

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, MS,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: FACTORIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2006
• First Posted: January 30, 2006
• Study Start: January 1, 2006
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: April 21, 2020
• Results First Posted: February 27, 2015

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share

Locations

US (7)