HALT Progression of Polycystic Kidney Disease Study A

Kidney, Polycystic Clinical Trial

— HALT PKD A  

Official title:

HALT Progression of Polycystic Kidney Disease Study A

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00283686
• Other study ID #: HALT PKD A
• 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 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; NCT01885559). 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.

Description:

• Specific Aims of Study A

To study the efficacy of angiotensin-converting-enzyme inhibitor (ACE-I) and angiotensin-receptor blockade (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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 558
• 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 per liter (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 imaging (Study A).

Related Conditions & MeSH terms

• Kidney Diseases
• Kidney, Polycystic
• Polycystic Kidney Diseases

Intervention

Drug:
• Lisinopril
Lisinopril titrated to 5mg, 10mg, 20mg, 40mg
• Telmisartan
Telmisartan/Placebo titrated to 40mg and 80mg, as tolerated by participants
• Placebo
Telmisartan/Placebo titrated to 40mg and 80mg, as tolerated by participants

Other:
• Standard Blood Pressure Control
Achieve standard blood pressure control of 120-130/70-80 mm Hg using step dosing specified in protocol of lisinopril, study drug, hydrochlorothiazide, metoprolol, or non-dihydropyridine and dihydropyridine calcium channel blockers (diltiazem), clonidine, minoxidil, hydralazine at the discretion of the investigator
• Low Blood Pressure Control
Achieve low blood pressure control of 95-110/60-75 mm Hg using step dosing specified in protocol of lisinopril, study drug, hydrochlorothiazide, metoprolol, or non-dihydropyridine and dihydropyridine calcium channel blockers (diltiazem), clonidine, minoxidil, hydralazine at the discretion of the investigator

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	Study A: Percent Annual Change in Total Kidney Volume	Annual percentage change in total kidney volume as assessed by abdominal magnetic resonance imaging (MRI) at baseline, 2 years, 4 years, and 5 years follow-up.	Baseline and 2-, 4- and 5-year follow-up
Secondary	Kidney Function (eGFR)	The estimated GFR was calculated by means of the Chronic Kidney Disease Epidemiology Collaboration equation with the use of central serum creatinine measurements.	Up to 96 months (6 month assessments)
Secondary	Albuminuria	Urine albumin excretion, centrally processed from 24 hour urine collection	Up to 96 months (assessed annually)
Secondary	Aldosterone	Urinary aldosterone excretion, centrally processed, 24 hour urine collection	Up to 96 months (assessed annually)
Secondary	Left Ventricular Mass Index	Left ventricular mass index (g/m^2) measured by MRI, centrally reviewed and measured	0, 24 months, 48 months, 60 months
Secondary	Renal Blood Flow	renal blood flow (mL/min/1.73 m^2) from MRI, centrally reviewed and measured. This outcome was more difficult to measure resulting in more missing data than other MRI outcomes such as total kidney volume (TKV) and left ventricular mass index (LVMI).	0, 24 months, 48 months, 60 months
Secondary	All-Cause Hospitalizations		Up to 96 months
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)	baseline, 12, 24, 36, 48, 60, 72, 84, and 96 months (assessed annually)
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)	baseline, 12, 24, 36, 48, 60, 72, 84, and 96 months (assessed annually)

External Links

•   Polycystic Kidney Disease Foundation Website