HALT Progression of Polycystic Kidney Disease Study B (HALT PKD B)

• ClinicalTrials.gov Identifier: NCT01885559
• Recruitment Status: Completed
• First Posted: June 25, 2013
• Results First Posted: March 10, 2015
• Last Update Posted: April 22, 2020
• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: Boehringer Ingelheim; Merck Sharp & Dohme LLC; Polycystic Kidney Disease Foundation; University of Pittsburgh; Washington University School of Medicine
• Information provided by (Responsible Party): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Kidney, Polycystic	Drug: Lisinopril; Drug: Telmisartan; Drug: Placebo	Phase 3

Detailed Description:

* 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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 486 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: HALT Progression of Polycystic Kidney Disease Study B
• Actual Study Start Date: January 2006
• Actual Primary Completion Date: June 2014
• Actual Study Completion Date: June 2014

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: ACE-I + placebo; Monotherapy of lisinopril and placebo. Standard blood pressure control of 110-130/80 mm Hg	Drug: Lisinopril; 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; Drug: Placebo; Placebo titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.; Other Name: Control
Active Comparator: ACE-I + ARB; Dual therapy of lisinopril and telmisartan treatments. Standard blood pressure control of 110-130/80 mm Hg.	Drug: Lisinopril; 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; Drug: Telmisartan; Telmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.; Other Name: ARB

Outcome Measures

Primary Outcome Measures :

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 Outcome Measures :

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)

Eligibility Criteria

• Ages Eligible for Study: 15 Years to 64 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

United States, Colorado

University of Colorado Health Sciences Center

Aurora, Colorado, United States, 800045

United States, Georgia

Emory University School of Medicine

Atlanta, Georgia, United States, 30322

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

United States, Massachusetts

Tufts University-New England Medical Center

Boston, Massachusetts, United States, 02111

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, Ohio

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

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

Boehringer Ingelheim

Merck Sharp & Dohme LLC

Polycystic Kidney Disease Foundation

University of Pittsburgh

Washington University School of Medicine

Investigators

• Study Chair: Robert Schrier, M.D.; University of Colorado, Denver
• Principal Investigator: 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
• Study Director: Marva Moxey-Mims, M.D.; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Principal Investigator: Charity G Moore, PhD; University of Pittsburgh

More Information

Additional Information:

Polycystic Kidney Disease Foundation Website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• ClinicalTrials.gov Identifier: NCT01885559
• Obsolete Identifiers: NCT00067977
• Other Study ID Numbers: HALT PKD B; U01DK062401 ( U.S. NIH Grant/Contract ); U01DK082230 ( U.S. NIH Grant/Contract )
• First Posted: June 25, 2013
• Results First Posted: March 10, 2015
• Last Update Posted: April 22, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data are available at the NIDDK Central Repository, https://repository.niddk.nih.gov/studies/halt-pkd/?query=halt%20pkd
• URL: https://repository.niddk.nih.gov/studies/halt-pkd/?query=halt%20pkd

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

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

Additional relevant MeSH terms:

Kidney Diseases; Polycystic Kidney Diseases; Urologic Diseases; Kidney Diseases, Cystic; Abnormalities, Multiple; Congenital Abnormalities; Ciliopathies; Genetic Diseases, Inborn; Telmisartan; Lisinopril; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Cardiotonic Agents; Protective Agents; Physiological Effects of Drugs