title: The HALT polycystic kidney disease trials: design and implementation.
abstract: OBJECTIVE
  Two HALT PKD trials will investigate interventions that potentially slow kidney disease progression in hypertensive autosomal dominant polycystic kidney disease (ADPKD) patients. Studies were designed in early and later stages of ADPKD to assess the impact of intensive blockade of the renin-angiotensin-aldosterone system and level of BP control on progressive renal disease. Design, settings, participants, and measurements: PKD-HALT trials are multicenter, randomized, double-blind, placebo-controlled trials studying 1018 hypertensive ADPKD patients enrolled over 3 yr with 4 to 8 yr of follow-up. In study A, 548 participants, estimated GFR (eGFR) of >60 ml/min per 1.73 m(2) were randomized to one of four arms in a 2-by-2 design: combination angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) therapy versus ACEi monotherapy at two levels of BP control. In study B, 470 participants, eGFR of 25 to 60 ml/min per 1.73 m2 compared ACEi/ARB therapy versus ACEi monotherapy, with BP control of 120 to 130/70 to 80 mmHg. Primary outcomes of studies A and B are MR-based percent change kidney volume and a composite endpoint of time to 50% reduction of baseline estimated eGFR, ESRD, or death, respectively.
  
  
  RESULTS
  This report describes design issues related to (1) novel endpoints such as kidney volume, (2) home versus office BP measures, and (3) the impact of RAAS inhibition on kidney and patient outcomes, safety, and quality of life.
  
  
  CONCLUSIONS
  HALT PKD will evaluate potential benefits of rigorous BP control and inhibition of the renin-angiotensin-aldosterone system on kidney disease progression in ADPKD.
authors.affiliation: Emory University School of Medicine, Atlanta, GA 30322, USA. Arlene_chapman@emory.org
authors.forename: Arlene B
authors.initials: AB
authors.lastname: Chapman
authors.forename: Vicente E
authors.initials: VE
authors.lastname: Torres
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Perrone
authors.forename: Theodore I
authors.initials: TI
authors.lastname: Steinman
authors.forename: Kyongtae T
authors.initials: KT
authors.lastname: Bae
authors.forename: J Philip
authors.initials: JP
authors.lastname: Miller
authors.forename: Dana C
authors.initials: DC
authors.lastname: Miskulin
authors.forename: Frederic
authors.initials: F
authors.lastname: Rahbari Oskoui
authors.forename: Amirali
authors.initials: A
authors.lastname: Masoumi
authors.forename: Marie C
authors.initials: MC
authors.lastname: Hogan
authors.forename: Franz T
authors.initials: FT
authors.lastname: Winklhofer
authors.forename: William
authors.initials: W
authors.lastname: Braun
authors.forename: Paul A
authors.initials: PA
authors.lastname: Thompson
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Meyers
authors.forename: Cass
authors.initials: C
authors.lastname: Kelleher
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schrier
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy; D007674:Kidney Diseases / Q000209:etiology* / Q000517:prevention & control*; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors