HALT Progression of Polycystic Kidney Disease (HALT PKD)

Condition(s) targeted: Kidney, Polycystic

Intervention: Lisinopril and Placebo (Drug); Lisinopril and Telmisartan (Drug); Lisinopril and Telmisartan (Drug); Lisinopril and Placebo (Drug); Lisinopril and Telmisartan (Drug); Lisinopril and Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Official(s) and/or principal investigator(s):
Robert Schrier, M.D., Study Chair, Affiliation: University of Colorado at Denver and Health Sciences Center
Arlene Chapman, M.D., Principal Investigator, Affiliation: Emory University
J. Philip Miller, A.B., Principal Investigator, Affiliation: Washington University School of Medicine
Ronald Perrone, M.D., Principal Investigator, Affiliation: Tufts University-New England Medical Center
Vicente Torres, M.D., Principal Investigator, Affiliation: Mayo Clinic
Catherine Meyers, M.D., Study Director, Affiliation: National Institute of Diabetes & Digestive & Kidney Diseases

Overall contact:
Robin Woltman, B.S., Phone: 314-362-1318, Email: robinw@wubios.wustl.edu

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.

Official title: Polycystic Kidney Disease-Treatment Network

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment, Efficacy Study

Primary outcome:

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.

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).

Minimum age: 15 Years. Maximum age: 64 Years. Gender(s): Both.

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).

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

University of Colorado Health Sciences Center, Denver (Aurora), Colorado 800045, United States; Recruiting
Judy McCarty, Phone: 877-765-9297, Email: halt.pkd@uchsc.edu
Pamela Morgan, R.N., Phone: 877-765-9297, Email: halt.pkd@uchsc.edu
Robert Schrier, M.D., Principal Investigator
Elwaleed Elhassan, M.D., Sub-Investigator

Emory University School of Medicine, Atlanta, Georgia 30322, United States; Recruiting
Stacie Hitchcock, Phone: 404-712-1235, Email: shitch2@emory.edu
Diane Watkins, Phone: (404) 712-1354, Email: dpwatki@emory.edu
Arlene Chapman, M.D., Principal Investigator
Frederic Rahbari-Oskoui, M.D., Sub-Investigator

University of Kansas Medical Center, Kansas City, Kansas 66160, United States; Recruiting
Pam Lanza, RN, Phone: 913-588-7609, Email: planza@kumc.edu
Darlene Baker, RN, Phone: 913-588-7609, Email: dbaker@kumc.edu
Franz Winklhofer, M.D., Principal Investigator
Jared Grantham, M.D., Sub-Investigator

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States; Recruiting
Bonnie Maxwell, R.N., Phone: 866-650-1815, Email: bmaxwel1@bidmc.harvard.edu
Theodore Steinman, M.D., Principal Investigator
Joshua Tarkan, M.D., Sub-Investigator

Tufts University-New England Medical Center, Boston, Massachusetts 02111, United States; Recruiting
Peachy Simon, BSN, RN, CNN, Phone: 866-846-2735, Email: psimon@tufts-nemc.org
Julie Driggs, RN, Phone: (866) 846-2735, Email: jdriggs@tufts-nemc.org
Ronald Perrone, M.D., Principal Investigator
Dana Miskulin, M.D., Sub-Investigator

Mayo Clinic, Rochester, Minnesota 55905, United States; Recruiting
Troy Ofstie, Phone: 888-630-2616, Email: troy.ofstie@mayo.edu
Otto Kris, RNC, Phone: 888-630-2616, Email: otto.kristine@mayo.edu
Vicente Torres, M.D., Principal Investigator
Marie Hogan, M.D., Sub-Investigator

Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States; Recruiting
Rita Spirko, R.N., Phone: 800-223-2273, Ext: 44680, Email: spirkor@ccf.org
William Braun, M.D., Principal Investigator
Brian Stephany, M.D., Sub-Investigator

HALT PKD Home Page

Polycystic Kidney Disease Foundation Website

National Institute of Diabetes & Digestive & Kidney Diseases Website

HALT PKD Study Brochure

HALT PKD Information for Physicians Brochure

Starting date: January 2006
Ending date: April 2013
Last updated: September 13, 2008