HALT Progression of Polycystic Kidney Disease Study B

Kidney, Polycystic Clinical Trial

— HALT PKD B  

Official title:

HALT Progression of Polycystic Kidney Disease Study B

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01885559
• Other study ID #: HALT PKD B
• Secondary ID: U01DK062401U01DK
• Status: Completed
• Phase: Phase 3
• Start date: January 2006
• Est. completion date: June 2014

Study information

• Verified date: April 2020
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 simultaneous 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 B will be followed for five-to-eight years, with the average length of follow-up being six and a half years.

Combination therapy will use angiotensin-converting-enzyme inhibitor (ACE-I) and an angiotensin-receptor blocker (ARB). Monotherapy will use ACE-I alone.

Description:

• 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 estimated Glomerular Filtration Rate (eGFR), end-state renal disease (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).

Other known NCT identifiers

• NCT00067977

Recruitment information / eligibility

• Status: Completed
• Enrollment: 486
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 64 Years

Eligibility

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 (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 ß-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 (MR) imaging (Study A).

Related Conditions & MeSH terms

• Kidney Diseases
• Kidney, Polycystic
• Polycystic Kidney Diseases

Intervention

Drug:
• Lisinopril
Lisinopril titrated to 5mg, 10mg, 20mg, 40mg as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.
• Telmisartan
Telmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.
• Placebo
Placebo titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	University of Colorado Health Sciences Center	Aurora	Colorado
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Tufts University-New England Medical Center	Boston	Massachusetts
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (6)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Boehringer Ingelheim, Merck Sharp & Dohme Corp., Polycystic Kidney Disease Foundation, University of Pittsburgh, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With 50% Reduction of Baseline eGFR, End Stage Renal Disease (ESRD, Initiation of Dialysis or Preemptive Transplant), or Death.		Patients followed for 5-8 years with average of 6.5 years follow up
Secondary	Albuminuria	Annual percent change in 24 hour urine albumin, centrally processed. Data from multiple years were analyzed with the primary focus on the change over time for the measure (from the slope of the model). The measure presented is the average annual percent change across the 8 years.	up to 8 years (annually assessed)
Secondary	Aldosterone	Annual percent change in urinary aldosterone, centrally processed measure. Data from multiple years were analyzed with the primary focus on the change over time for the measure (from the slope for time from the model). The measure presented is the average annual percent change across the 8 years.	up at 8 years (annually assessed)
Secondary	Hospitalizations	Hospitalization for any cause	up to 8 years
Secondary	Cardiovascular Hospitalizations	Cause-specific hospitalizations (cardiovascular)	up to 8 years
Secondary	Quality of Life Physical Component Summary	Short Form-36 Quality of Life Physical Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome). Data from multiple years were analyzed with the primary focus on the change over time for the measure (from the slope for time from the model). The measure presented is the average annual change across the 8 years.	up to 8 years (annually assessed)
Secondary	Quality of Life Mental Component Summary	Short Form-36 Quality of Life Mental Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome). Data from multiple years were analyzed with the primary focus on the change over time for the measure (from the slope for time from the model). The measure presented is the average annual change across the 8 years.	up to 8 years (annually assessed)
Secondary	Back or Flank Pain	Report of back or flank pain since the last visit (yes or no)	48 months

External Links

•   Polycystic Kidney Disease Foundation Website