Design and statistical issues in the homocysteinemia in kidney and end stage renal disease (HOST) study.
The Homocysteine Study (HOST) Veterans Affairs Cooperative Studies Program No. 453, is a prospective, randomized, two arm, double blind study of patients with end stage renal disease (ESRD) or advanced chronic kidney disease (ACKD, defined as an estimated creatinine clearance of 30 ml/min or less). Its primary objective is to determine whether administration of high doses of three vitamins, folic acid, vitamin B6 and vitamin B12, to lower the high plasma homocysteine levels, will reduce all cause mortality. The secondary objectives are to examine whether the treatment lowers the incidence of myocardial infarction, stroke, amputation of a lower extremity, a composite of death and the foregoing three events, the plasma homocysteine level, and, in ESRD patients undergoing hemodialysis, thrombosis of the vascular access. A unique feature of this trial is that after initial evaluation at enrollment and one return visit the follow up is exclusively by phone (or, if necessary, by mail). The subject is contacted every three months throughout the duration of the study from a central location. The study drug is shipped to the patient from a central location rather supplied locally. In a two year enrollment period, 2006 patients are to be enrolled. The duration of the observation period is four to six years. Data will be stored and analyzed at a coordinating center. The study design has the power to detect a reduction in all cause mortality rate of 17%. Issues related to the unique features of the design of this study are discussed.
Jamison
Rex L
RL
Division of Nephrology, Stanford University School of Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA.
Hartigan
Pamela
P
Gaziano
J Michael
JM
Fortmann
Stephen P
SP
Goldfarb
David S
DS
Haroldson
Jeffrey A
JA
Kaufman
James
J
Lavori
Philip
P
McCully
Kilmer S
KS
Robinson
Killian
K
D000328:Adult; D002423:Cause of Death; D004311:Double-Blind Method; D005492:Folic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood / Q000187:drug effects*; D006787:Hospitals, Veterans; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000379:methods*; D018579:Patient Selection; D011446:Prospective Studies; D011736:Pyridoxine / Q000008:administration & dosage / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D006435:Renal Dialysis / Q000009:adverse effects; D012107:Research Design; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000627:therapeutic use*
D006710:Homocysteine; D005492:Folic Acid; D011736:Pyridoxine; D014805:Vitamin B 12