HALT Progression of Polycystic Kidney Disease (HALT PKD)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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). 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Kidney, Polycystic |
Drug: Lisinopril and Placebo Drug: Lisinopril and Telmisartan |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Polycystic Kidney Disease-Treatment Network |
- Study A: Change in total kidney volume, as assessed by abdominal MR 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 ]
- Study B: Time to the 50% reduction of baseline eGFR, ESRD (initiation of dialysis or preemptive transplant), or death. [ Time Frame: As noted above ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 1018 |
| Study Start Date: | January 2006 |
| Estimated Study Completion Date: | June 2014 |
| Estimated Primary Completion Date: | June 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Study A, Arm 1
ACE-I + ARB and standard blood pressure control of 120-130/70-80 mm Hg
|
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:
|
|
Active Comparator: Study A, Arm 2
ACE-I + ARB and low blood pressure control of 95-110/60-75 mm Hg
|
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:
|
|
Placebo Comparator: Study A, Arm 3
ACE-I + Placebo and standard blood pressure control of 120-130/70-80 mm Hg
|
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:
|
|
Placebo Comparator: Study A, Arm 4
ACE-I + Placebo and low blood pressure control of 95-110/60-75 mm Hg
|
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:
|
|
Active Comparator: Study B, Arm 1
ACE-I + ARB and standard blood pressure control of 110-130/80 mm Hg
|
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 110-130/80 mm Hg.
Other Names:
|
|
Placebo Comparator: Study B, Arm 2
ACE-I + placebo and standard blood pressure control of 110-130/80 mm Hg
|
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 110-130/80 mm Hg.
Other Names:
|
Detailed Description:
* Specific Aims of Study A
To study the efficacy of ACE-I/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.
* 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 eGFR, 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).
Eligibility| Ages Eligible for Study: | 15 Years to 64 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 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 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 MR imaging (Study A).
Contacts and Locations| United States, Colorado | |
| University of Colorado Health Sciences Center | |
| Denver (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 | |
| Beth Israel Deaconess Medical Center | |
| Boston, Massachusetts, United States, 02215 | |
| Tufts University-New England Medical Center | |
| Boston, Massachusetts, United States, 02111 | |
| United States, Minnesota | |
| Mayo Clinic | |
| Rochester, Minnesota, United States, 55905 | |
| United States, Ohio | |
| Cleveland Clinic Foundation | |
| Cleveland, Ohio, United States, 44195 | |
| 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 |
More Information
Additional Information:
No publications provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Dr. Catherine Meyers, Director, Inflammatory Renal Diseases Program, National Institute of Diabetes and Digestive and Kidney Diseases |
| ClinicalTrials.gov Identifier: | NCT00283686 History of Changes |
| Other Study ID Numbers: | DK62401-PKD-TN (IND) |
| Study First Received: | January 26, 2006 |
| Last Updated: | April 28, 2013 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board United States: Federal Government |
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 Angiotensin-Converting Enzyme Inhibitors Lisinopril Telmisartan Benzoates Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
Pharmacologic Actions Antihypertensive Agents Cardiovascular Agents Therapeutic Uses Cardiotonic Agents Protective Agents Physiological Effects of Drugs Angiotensin II Type 1 Receptor Blockers Angiotensin Receptor Antagonists Antifungal Agents Anti-Infective Agents |
ClinicalTrials.gov processed this record on May 23, 2013