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

Primary Purpose

Kidney, Polycystic

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Lisinopril

Telmisartan

Placebo

About this trial

This is an interventional treatment trial for Kidney, Polycystic focused on measuring polycystic kidney disease, polycystic, kidney, disease, adpkd, halt, pkd, blood pressure, bp, hypertension, renal, renin-angiotensin-aldosterone-system, RAAS

Eligibility Criteria

15 Years - 64 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

University of Colorado Health Sciences Center
Emory University School of Medicine
University of Kansas Medical Center
Tufts University-New England Medical Center
Beth Israel Deaconess Medical Center
Mayo Clinic
Cleveland Clinic Foundation

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

ACE-I + placebo

ACE-I + ARB

Arm Description

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

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

Outcomes

Primary Outcome Measures

Number of Participants With 50% Reduction of Baseline eGFR, End Stage Renal Disease (ESRD, Initiation of Dialysis or Preemptive Transplant), or Death.

Secondary Outcome Measures

Albuminuria

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.

Aldosterone

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.

Hospitalizations

Hospitalization for any cause

Cardiovascular Hospitalizations

Cause-specific hospitalizations (cardiovascular)

Quality of Life Physical Component Summary

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.

Quality of Life Mental Component Summary

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.

Back or Flank Pain

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

Full Information

NCT ID

NCT01885559

First Posted

June 17, 2013

Last Updated

April 13, 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

1. Study Identification

Unique Protocol Identification Number

NCT01885559

Brief Title

HALT Progression of Polycystic Kidney Disease Study B

Acronym

HALT PKD B

Official Title

HALT Progression of Polycystic Kidney Disease Study B

Study Type

Interventional

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Completed

Study Start Date

January 2006 (Actual)

Primary Completion Date

June 2014 (Actual)

Study Completion Date

June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the 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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Kidney, Polycystic

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

486 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ACE-I + placebo

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

ACE-I + ARB

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Lisinopril

Other Intervention Name(s)

ACE-I, ACE, Ace-Inhibitor

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Telmisartan

Other Intervention Name(s)

ARB

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Control

Intervention Description

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

Primary Outcome Measure Information:

Title

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 Measure Information:

Title

Albuminuria

Description

Time Frame

up to 8 years (annually assessed)

Title

Aldosterone

Description

Time Frame

up at 8 years (annually assessed)

Title

Hospitalizations

Description

Hospitalization for any cause

Time Frame

up to 8 years

Title

Cardiovascular Hospitalizations

Description

Cause-specific hospitalizations (cardiovascular)

Time Frame

up to 8 years

Title

Quality of Life Physical Component Summary

Description

Time Frame

up to 8 years (annually assessed)

Title

Quality of Life Mental Component Summary

Description

Time Frame

up to 8 years (annually assessed)

Title

Back or Flank Pain

Description

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

Time Frame

48 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

15 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

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 <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).

Overall Study Officials: