Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Collaborators:
Boehringer Ingelheim
Merck Sharp & Dohme Corp.
Polycystic Kidney Disease Foundation
Information provided by (Responsible Party):
Charity G Moore, PhD, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00283686
First received: January 26, 2006
Last updated: February 25, 2015
Last verified: February 2015

January 26, 2006
February 25, 2015
January 2006
June 2014   (final data collection date for primary outcome measure)
Study A: Percent Annual Change in Total Kidney Volume, as Assessed by Abdominal Magnetic Resonance Imaging (MRI) at Baseline, 2 Years, and 4 Years Follow-up. [ Time Frame: Baseline and 2-, 4- and 5-year follow-up ] [ Designated as safety issue: No ]
Annual percentage change in total kidney volume from linear mixed-effects models adjusting for age, sex, race, baseline estimate GFR, and clinical site.
  • - 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.
Complete list of historical versions of study NCT00283686 on ClinicalTrials.gov Archive Site
  • Kidney Function (eGFR) [ Time Frame: Up to 96 months (6 month assessments) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    Urine albumin excretion, centrally processed from 24 hour urine collection
  • Aldosterone [ Time Frame: Up to 96 months (assessed annually) ] [ Designated as safety issue: No ]
    Urinary aldosterone excretion, centrally processed, 24 hour urine collection
  • Left Ventricular Mass Index [ Time Frame: 0, 24 months, 48 months, 60 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Quality of Life Physical Component Summary [ Time Frame: Up to 96 months (assessed annually) ] [ Designated as safety issue: No ]
    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: up to 96 months (assessed annually) ] [ Designated as safety issue: No ]
    Short Form-36 Quality of LIfe Mental Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome)
Not Provided
Not Provided
Not Provided
 
HALT Progression of Polycystic Kidney Disease (HALT PKD) Study A
Polycystic Kidney Disease-Treatment Network

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.

* 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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Kidney, Polycystic
  • Drug: Lisinopril and Placebo
    Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and placebo titrated to 40mg and 80mg, as tolerated by participants, to achieve low blood pressure control of 95-110/60-75 mm Hg.
    Other Names:
    • ACE-I
    • ACE
    • Ace-Inhibitor
    • Lisinopril
    • ARB
    • Placebo
  • Drug: Lisinopril and Telmisartan
    Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and telmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 120-130/70-80 mm Hg.
    Other Names:
    • ACE-I
    • ACE
    • Ace-Inhibitor
    • Lisinopril
    • ARB
    • Telmisartan
  • Drug: Lisinopril and Telmisartan
    Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and telmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve low blood pressure control of 95-110/60-75 mm Hg.
    Other Names:
    • ACE-I
    • ACE
    • Ace-Inhibitor
    • Lisinopril
    • ARB
    • Telmisartan
  • Drug: Lisinopril and Placebo
    Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and placebo titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 120-130/70-80 mm Hg.
    Other Names:
    • ACE-I
    • ACE
    • Ace-Inhibitor
    • Lisinopril
    • ARB
    • Placebo
  • Active Comparator: Study A, Arm 1
    ACE-I + ARB and standard blood pressure control of 120-130/70-80 mm Hg
    Intervention: Drug: Lisinopril and Telmisartan
  • Active Comparator: Study A, Arm 2
    ACE-I + ARB and low blood pressure control of 95-110/60-75 mm Hg
    Intervention: Drug: Lisinopril and Telmisartan
  • Placebo Comparator: Study A, Arm 3
    ACE-I + Placebo and standard blood pressure control of 120-130/70-80 mm Hg
    Intervention: Drug: Lisinopril and Placebo
  • Placebo Comparator: Study A, Arm 4
    ACE-I + Placebo and low blood pressure control of 95-110/60-75 mm Hg
    Intervention: Drug: Lisinopril and Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
558
June 2014
June 2014   (final data collection date for primary outcome measure)

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).
Both
15 Years to 64 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00283686
DK62401-PKD-TN (IND)
Yes
Charity G Moore, PhD, University of Pittsburgh
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Boehringer Ingelheim
  • Merck Sharp & Dohme Corp.
  • Polycystic Kidney Disease Foundation
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
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
February 2015

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