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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00283686
Recruitment Status : Completed
First Posted : January 30, 2006
Results First Posted : February 27, 2015
Last Update Posted : March 19, 2015
Sponsor:
Collaborators:
Boehringer Ingelheim
Merck Sharp & Dohme Corp.
Polycystic Kidney Disease Foundation
Information provided by (Responsible Party):
Charity G Moore, PhD, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE January 26, 2006
First Posted Date  ICMJE January 30, 2006
Results First Submitted Date  ICMJE February 9, 2015
Results First Posted Date  ICMJE February 27, 2015
Last Update Posted Date March 19, 2015
Study Start Date  ICMJE January 2006
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2015)
Study A: Percent Annual Change in Total Kidney Volume [ Time Frame: Baseline and 2-, 4- and 5-year follow-up ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 26, 2006)
  • - Study A: Change in total kidney volume, as assessed by abdominal MR at baseline, 2 years, and 4 years follow-up.
  • - Study B: Time to the 50% reduction of baseline eGFR, ESRD (initiation of dialysis or preemptive transplant), or death.
Change History Complete list of historical versions of study NCT00283686 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2015)
  • Kidney Function (eGFR) [ Time Frame: Up to 96 months (6 month assessments) ]
    The estimated GFR was calculated by means of the Chronic Kidney Disease Epidemiology Collaboration equation with the use of central serum creatinine measurements.
  • Albuminuria [ Time Frame: Up to 96 months (assessed annually) ]
    Urine albumin excretion, centrally processed from 24 hour urine collection
  • Aldosterone [ Time Frame: Up to 96 months (assessed annually) ]
    Urinary aldosterone excretion, centrally processed, 24 hour urine collection
  • Left Ventricular Mass Index [ Time Frame: 0, 24 months, 48 months, 60 months ]
    Left ventricular mass index (g/m^2) measured by MRI, centrally reviewed and measured
  • Renal Blood Flow [ Time Frame: 0, 24 months, 48 months, 60 months ]
    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 [ Time Frame: Up to 96 months ]
  • Quality of Life Physical Component Summary [ Time Frame: baseline, 12, 24, 36, 48, 60, 72, 84, and 96 months (assessed annually) ]
    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 [ Time Frame: baseline, 12, 24, 36, 48, 60, 72, 84, and 96 months (assessed annually) ]
    Short Form-36 Quality of LIfe Mental Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome)
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE HALT Progression of Polycystic Kidney Disease (HALT PKD) Study A
Official Title  ICMJE Polycystic Kidney Disease-Treatment Network
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Kidney, Polycystic
Intervention  ICMJE
  • Drug: Lisinopril
    Lisinopril titrated to 5mg, 10mg, 20mg, 40mg
    Other Names:
    • ACE-I
    • ACE
    • Ace-Inhibitor
  • Drug: Telmisartan
    Telmisartan/Placebo titrated to 40mg and 80mg, as tolerated by participants
    Other Name: ARB
  • Drug: Placebo
    Telmisartan/Placebo titrated to 40mg and 80mg, as tolerated by participants
  • Other: Standard Blood Pressure Control
    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
    Other Name: blood pressure control
  • Other: Low Blood Pressure Control
    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
    Other Name: blood pressure control
Study Arms  ICMJE
  • Active Comparator: Study A, Arm 1
    Lisinopril + Telmisartan (ACE-I + ARB) and standard blood pressure control of 120-130/70-80 mm Hg
    Interventions:
    • Drug: Lisinopril
    • Drug: Telmisartan
    • Other: Standard Blood Pressure Control
  • Active Comparator: Study A, Arm 2
    Lisinopril + Telmisartan (ACE-I + ARB) and low blood pressure control of 95-110/60-75 mm Hg
    Interventions:
    • Drug: Lisinopril
    • Drug: Telmisartan
    • Other: Low Blood Pressure Control
  • Placebo Comparator: Study A, Arm 3
    Lisinopril + Placebo (ACE-I + Placebo) and standard blood pressure control of 120-130/70-80 mm Hg
    Interventions:
    • Drug: Lisinopril
    • Drug: Placebo
    • Other: Standard Blood Pressure Control
  • Placebo Comparator: Study A, Arm 4
    Lisinopril + Placebo (ACE-I + Placebo) and low blood pressure control of 95-110/60-75 mm Hg
    Interventions:
    • Drug: Lisinopril
    • Drug: Placebo
    • Other: Low Blood Pressure Control
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 25, 2015)
558
Original Enrollment  ICMJE
 (submitted: January 26, 2006)
1018
Actual Study Completion Date  ICMJE June 2014
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years to 64 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00283686
Other Study ID Numbers  ICMJE DK62401-PKD-TN (IND)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Charity G Moore, PhD, University of Pittsburgh
Study Sponsor  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators  ICMJE
  • Boehringer Ingelheim
  • Merck Sharp & Dohme Corp.
  • Polycystic Kidney Disease Foundation
Investigators  ICMJE
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, MS,PhD University of Pittsburgh
PRS Account National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Verification Date March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP