HALT Progression of Polycystic Kidney Disease Study A
Condition: Kidney, Polycystic
MeSH terms: Kidney Diseases; Polycystic Kidney Diseases
Study type: Interventional
Phase: Phase 3

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.
    

Detailed 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.
    

Intervention name(s): Lisinopril; Telmisartan; Placebo; Standard Blood Pressure Control; Low Blood Pressure Control
Intervention type(s): Drug; Drug; Drug; Other; Other
Intervention description(s): Lisinopril titrated to 5mg, 10mg, 20mg, 40mg; Telmisartan/Placebo titrated to 40mg and 80mg, as tolerated by participants; Telmisartan/Placebo titrated to 40mg and 80mg, as tolerated by participants; 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; 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
Other intervention name(s): ACE-I; ACE; Ace-Inhibitor; ARB; blood pressure control; blood pressure control
Intervention MeSH terms: Telmisartan; Lisinopril; Angiotensin-Converting Enzyme Inhibitors
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: polycystic kidney disease; polycystic; kidney; disease; adpkd; halt; pkd; blood pressure; bp; hypertension; renal; renin-angiotensin-aldosterone-system; RAAS