Clincal trials: HALT Progression of Polycystic Kidney Disease (HALT PKD)

HALT Progression of Polycystic Kidney Disease (HALT PKD)

This study is currently recruiting participants.
Verified by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), September 2008

Sponsors and Collaborators:    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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

Genetics Home Reference related topics:     polycystic kidney disease

ChemIDplus related topics:     Lisinopril Telmisartan Aldosterone

U.S. FDA Resources

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

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

Contacts
Contact: Robin Woltman, B.S.     314-362-1318     robinw@wubios.wustl.edu

Locations
United States, Colorado
   University of Colorado Health Sciences Center        Recruiting
     Denver (Aurora), Colorado, United States, 800045
     Contact: Judy McCarty 877-765-9297 halt.pkd@uchsc.edu
     Contact: Pamela Morgan, R.N. 877-765-9297 halt.pkd@uchsc.edu
     Principal Investigator: Robert Schrier, M.D.
     Sub-Investigator: Elwaleed Elhassan, M.D.
United States, Georgia
   Emory University School of Medicine        Recruiting
     Atlanta, Georgia, United States, 30322
     Contact: Stacie Hitchcock 404-712-1235 shitch2@emory.edu
     Contact: Diane Watkins (404) 712-1354 dpwatki@emory.edu
     Principal Investigator: Arlene Chapman, M.D.
     Sub-Investigator: Frederic Rahbari-Oskoui, M.D.
United States, Kansas
   University of Kansas Medical Center        Recruiting
     Kansas City, Kansas, United States, 66160
     Contact: Pam Lanza, RN 913-588-7609 planza@kumc.edu
     Contact: Darlene Baker, RN 913-588-7609 dbaker@kumc.edu
     Principal Investigator: Franz Winklhofer, M.D.
     Sub-Investigator: Jared Grantham, M.D.
United States, Massachusetts
   Beth Israel Deaconess Medical Center        Recruiting
     Boston, Massachusetts, United States, 02215
     Contact: Bonnie Maxwell, R.N. 866-650-1815 bmaxwel1@bidmc.harvard.edu
     Principal Investigator: Theodore Steinman, M.D.
     Sub-Investigator: Joshua Tarkan, M.D.
   Tufts University-New England Medical Center        Recruiting
     Boston, Massachusetts, United States, 02111
     Contact: Peachy Simon, BSN, RN, CNN 866-846-2735 psimon@tufts-nemc.org
     Contact: Julie Driggs, RN (866) 846-2735 jdriggs@tufts-nemc.org
     Principal Investigator: Ronald Perrone, M.D.
     Sub-Investigator: Dana Miskulin, M.D.
United States, Minnesota
   Mayo Clinic        Recruiting
     Rochester, Minnesota, United States, 55905
     Contact: Troy Ofstie 888-630-2616 troy.ofstie@mayo.edu
     Contact: Otto Kris, RNC 888-630-2616 otto.kristine@mayo.edu
     Principal Investigator: Vicente Torres, M.D.
     Sub-Investigator: Marie Hogan, M.D.
United States, Ohio
   Cleveland Clinic Foundation        Recruiting
     Cleveland, Ohio, United States, 44195
     Contact: Rita Spirko, R.N. 800-223-2273 ext 44680 spirkor@ccf.org
     Principal Investigator: William Braun, M.D.
     Sub-Investigator: Brian Stephany, M.D.

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:     Catherine Meyers, M.D.     National Institute of Diabetes & Digestive & Kidney Diseases
More 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

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
First Received:     January 26, 2006
Last Updated:     September 13, 2008
ClinicalTrials.gov Identifier:     NCT00283686
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
kidney
renal
polycystic
disease
adpkd
halt

pkd
blood pressure
bp
hypertension
renin-angiotensin-aldosterone-system
RAAS

Study placed in the following topic categories:
Urologic Diseases
Lisinopril
Kidney Diseases, Cystic
Disease Progression
Polycystic Kidney Diseases

Telmisartan
Kidney Diseases
Angiotensin II
Hypertension

Additional relevant MeSH terms:
Angiotensin II Type 1 Receptor Blockers
Molecular Mechanisms of Pharmacological Action
Cardiotonic Agents
Therapeutic Uses
Physiological Effects of Drugs
Angiotensin-Converting Enzyme Inhibitors

Enzyme Inhibitors
Cardiovascular Agents
Antihypertensive Agents
Protective Agents
Pharmacologic Actions
Protease Inhibitors

ClinicalTrials.gov processed this record on September 23, 2008
http://clinicaltrials.gov/ct2/show/NCT00283686