Back to resultsHALT Progression of Polycystic Kidney Disease Study A (HALT PKD A)
Primary Purpose
Kidney, Polycystic
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Lisinopril
Telmisartan
Placebo
Standard Blood Pressure Control
Low Blood Pressure Control
Sponsored by
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
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 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). Known allergy to sorbitol or sodium polystyrene sulfonate. Exclusions specific to magnetic resonance 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 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Placebo Comparator
Arm Label
Study A, Arm 1
Study A, Arm 2
Study A, Arm 3
Study A, Arm 4
Arm Description
Lisinopril + Telmisartan (ACE-I + ARB) and standard blood pressure control of 120-130/70-80 mm Hg
Lisinopril + Telmisartan (ACE-I + ARB) and low blood pressure control of 95-110/60-75 mm Hg
Lisinopril + Placebo (ACE-I + Placebo) and standard blood pressure control of 120-130/70-80 mm Hg
Lisinopril + Placebo (ACE-I + Placebo) and low blood pressure control of 95-110/60-75 mm Hg
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Kidney Function (eGFR)
The estimated GFR was calculated by means of the Chronic Kidney Disease Epidemiology Collaboration equation with the use of central serum creatinine measurements.
Albuminuria
Urine albumin excretion, centrally processed from 24 hour urine collection
Aldosterone
Urinary aldosterone excretion, centrally processed, 24 hour urine collection
Left Ventricular Mass Index
Left ventricular mass index (g/m^2) measured by MRI, centrally reviewed and measured
Renal Blood Flow
renal blood flow (mL/min/1.73 m^2) from MRI, centrally reviewed and measured. This outcome was more difficult to measure resulting in more missing data than other MRI outcomes such as total kidney volume (TKV) and left ventricular mass index (LVMI).
All-Cause Hospitalizations
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)
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)
Full Information
NCT ID
NCT00283686
First Posted
January 26, 2006
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
NCT00283686
Brief Title
HALT Progression of Polycystic Kidney Disease Study A
Acronym
HALT PKD A
Official Title
HALT Progression of Polycystic Kidney Disease Study A
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
No
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 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.
Detailed Description
* Specific Aims of Study A
To study the efficacy of angiotensin-converting-enzyme inhibitor (ACE-I) and angiotensin-receptor blockade (ARB) combination therapy as compared to ACE-I monotherapy and usual vs. low blood pressure targets on the percent change in kidney volume in participants with preserved renal function (GFR >60 mL/min/1.73m2)and high-normal blood pressure or hypertension (>130/80 mm Hg).
* Hypotheses to be tested in Study A
In ADPKD individuals with hypertension or high-normal blood pressure and relatively preserved renal function (GFR >60 mL/min/1.73 m2), multi-level blockade of the RAAS using ACE-I/ARB combination therapy will delay progression of cystic disease as compared to ACE-I monotherapy, and a low blood pressure goal will delay progression as compared with standard control.
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
Factorial Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
558 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Study A, Arm 1
Arm Type
Active Comparator
Arm Description
Lisinopril + Telmisartan (ACE-I + ARB) and standard blood pressure control of 120-130/70-80 mm Hg
Arm Title
Study A, Arm 2
Arm Type
Active Comparator
Arm Description
Lisinopril + Telmisartan (ACE-I + ARB) and low blood pressure control of 95-110/60-75 mm Hg
Arm Title
Study A, Arm 3
Arm Type
Placebo Comparator
Arm Description
Lisinopril + Placebo (ACE-I + Placebo) and standard blood pressure control of 120-130/70-80 mm Hg
Arm Title
Study A, Arm 4
Arm Type
Placebo Comparator
Arm Description
Lisinopril + Placebo (ACE-I + Placebo) and low blood pressure control of 95-110/60-75 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
Intervention Type
Drug
Intervention Name(s)
Telmisartan
Other Intervention Name(s)
ARB
Intervention Description
Telmisartan/Placebo titrated to 40mg and 80mg, as tolerated by participants
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Telmisartan/Placebo titrated to 40mg and 80mg, as tolerated by participants
Intervention Type
Other
Intervention Name(s)
Standard Blood Pressure Control
Other Intervention Name(s)
blood pressure control
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Low Blood Pressure Control
Other Intervention Name(s)
blood pressure control
Intervention Description
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
Primary Outcome Measure Information:
Title
Study A: Percent Annual Change in Total Kidney Volume
Description
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.
Time Frame
Baseline and 2-, 4- and 5-year follow-up
Secondary Outcome Measure Information:
Title
Kidney Function (eGFR)
Description
The estimated GFR was calculated by means of the Chronic Kidney Disease Epidemiology Collaboration equation with the use of central serum creatinine measurements.
Time Frame
Up to 96 months (6 month assessments)
Title
Albuminuria
Description
Urine albumin excretion, centrally processed from 24 hour urine collection
Time Frame
Up to 96 months (assessed annually)
Title
Aldosterone
Description
Urinary aldosterone excretion, centrally processed, 24 hour urine collection
Time Frame
Up to 96 months (assessed annually)
Title
Left Ventricular Mass Index
Description
Left ventricular mass index (g/m^2) measured by MRI, centrally reviewed and measured
Time Frame
0, 24 months, 48 months, 60 months
Title
Renal Blood Flow
Description
renal blood flow (mL/min/1.73 m^2) from MRI, centrally reviewed and measured. This outcome was more difficult to measure resulting in more missing data than other MRI outcomes such as total kidney volume (TKV) and left ventricular mass index (LVMI).
Time Frame
0, 24 months, 48 months, 60 months
Title
All-Cause Hospitalizations
Time Frame
Up to 96 months
Title
Quality of Life Physical Component Summary
Description
Short Form-36 Quality of Life Physical Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome)
Time Frame
baseline, 12, 24, 36, 48, 60, 72, 84, and 96 months (assessed annually)
Title
Quality of Life Mental Component Summary
Description
Short Form-36 Quality of LIfe Mental Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome)
Time Frame
baseline, 12, 24, 36, 48, 60, 72, 84, and 96 months (assessed annually)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
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 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).
Known allergy to sorbitol or sodium polystyrene sulfonate.
Exclusions specific to magnetic resonance imaging (Study A).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Schrier, M.D.
Organizational Affiliation
University of Colorado, Denver
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Arlene Chapman, M.D.
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ronald Perrone, M.D.
Organizational Affiliation
Tufts University-New England Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Vicente Torres, M.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marva Moxey-Mims, M.D.
Organizational Affiliation
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Charity G Moore, MS,PhD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado Health Sciences Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
800045
Country
United States
Facility Name
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Tufts University-New England Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data are available at the NIDDK Central Repository, https://repository.niddk.nih.gov/studies/halt-pkd/?query=halt%20pkd
IPD Sharing URL
https://repository.niddk.nih.gov/studies/halt-pkd/?query=halt%20pkd
Citations:
PubMed Identifier
30803434
Citation
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.
Results Reference
derived
PubMed Identifier
25399733
Citation
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.
Results Reference
derived
PubMed Identifier
25111236
Citation
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.
Results Reference
derived
PubMed Identifier
22205355
Citation
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.
Results Reference
derived
Links:
URL
http://www.pkdcure.org
Description
Polycystic Kidney Disease Foundation Website
Learn more about this trial
HALT Progression of Polycystic Kidney Disease Study A
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