HALT Progression of Polycystic Kidney Disease (HALT PKD) - Full Text View

Sponsor:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators:	Boehringer Ingelheim Pharmaceuticals Merck Polycystic Kidney Disease Foundation
Information provided by:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT00283686

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 a total of four years, while those enrolled in Study B will be followed for four-to-six years, with the average length of follow-up being five 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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment, Efficacy Study
Official Title:	Polycystic Kidney Disease-Treatment Network

Resource links provided by NLM:

Genetics Home Reference related topics: polycystic kidney disease

Drug Information available for: Lisinopril Telmisartan

U.S. FDA Resources

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:

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- and 4-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:	April 2013
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Study A, Arm 1: Active Comparator 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.
Study A, Arm 2: Active Comparator 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.
Study A, Arm 3: Placebo Comparator 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.
Study A, Arm 4: Placebo Comparator 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.
Study B, Arm 1: Active Comparator 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.
Study B, Arm 2: Placebo Comparator 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.

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

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 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00283686

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

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Boehringer Ingelheim Pharmaceuticals

Merck

Polycystic Kidney Disease Foundation

Investigators

Study Chair:	Robert Schrier, M.D.	University of Colorado at Denver and Health Sciences Center
Principal Investigator:	Arlene Chapman, M.D.	Emory University
Principal Investigator:	J. Philip Miller, A.B.	Washington University School of Medicine
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 & Digestive & Kidney Diseases
Principal Investigator:	James E Bost, MS,PhD	University of Pittsburgh

More Information

Additional Information:

HALT PKD Home Page This link exits the ClinicalTrials.gov site

Polycystic Kidney Disease Foundation Website This link exits the ClinicalTrials.gov site

National Institute of Diabetes & Digestive & Kidney Diseases Website This link exits the ClinicalTrials.gov site

HALT PKD Study Brochure This link exits the ClinicalTrials.gov site

HALT PKD Information for Physicians Brochure This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	National Institute of Diabetes and Digestive and Kidney Diseases ( Dr. Catherine Meyers, Director, Inflammatory Renal Diseases Program )
Study ID Numbers:	DK62401-PKD-TN
Study First Received:	January 26, 2006
Last Updated:	August 6, 2009
ClinicalTrials.gov Identifier:	NCT00283686 History of Changes
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:

Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Cardiotonic Agents
Benzoates
Physiological Effects of Drugs
Kidney Diseases, Cystic
Lisinopril
Polycystic Kidney Diseases
Enzyme Inhibitors
Cardiovascular Agents
Antihypertensive Agents

Protective Agents
Pharmacologic Actions
Protease Inhibitors
Angiotensin II Type 1 Receptor Blockers
Urologic Diseases
Antifungal Agents
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Kidney Diseases
Telmisartan

ClinicalTrials.gov processed this record on November 09, 2009