The Age of Red Blood Cells in Premature Infants (ARIPI) Randomized Controlled Trial: Study Design

Fergusson, Dean; Hutton, Brian; Hogan, Debora L.; LeBel, Louise; Blajchman, Morris A.; Ford, Jason C.; Hebert, Paul; Kakadekar, Ashok; Kovacs, Lajos; Lee, Shoo; Sankaran, Koravangattu; Shapiro, Stan; Smyth, John A.; Ramesh, Kuppuchipalayam; Bouali, Nicole Rouvinez; Tinmouth, Alan; Walker, Robin

doi:10.1016/j.tmrv.2008.09.005

« Previous Next »Transfusion Medicine Reviews
Volume 23, Issue 1 , Pages 55-61, January 2009

The Age of Red Blood Cells in Premature Infants (ARIPI) Randomized Controlled Trial: Study Design

Dean Fergusson
- Address reprint requests to Dean Fergusson, MHA, PhD, Clinical Epidemiology Program, The Ottawa Hospital, 501 Smyth Rd, Box 201, Ottawa, Ontario, Canada K1H 8L6.
- Authors DF, BH, DH, MB, PH, LK, SL, KS, SS, AT and RW all provided significant contributions to the development of the study protocol in its development phase, and all are involved in this ongoing study in the role of either site investigator, site coordinator or steering committee member.
Brian Hutton
- Authors DF, BH, DH, MB, PH, LK, SL, KS, SS, AT and RW all provided significant contributions to the development of the study protocol in its development phase, and all are involved in this ongoing study in the role of either site investigator, site coordinator or steering committee member.
Debora L. Hogan
- Authors DF, BH, DH, MB, PH, LK, SL, KS, SS, AT and RW all provided significant contributions to the development of the study protocol in its development phase, and all are involved in this ongoing study in the role of either site investigator, site coordinator or steering committee member.
Louise LeBel
Morris A. Blajchman
- Authors DF, BH, DH, MB, PH, LK, SL, KS, SS, AT and RW all provided significant contributions to the development of the study protocol in its development phase, and all are involved in this ongoing study in the role of either site investigator, site coordinator or steering committee member.
Jason C. Ford
Paul Hebert
- Authors DF, BH, DH, MB, PH, LK, SL, KS, SS, AT and RW all provided significant contributions to the development of the study protocol in its development phase, and all are involved in this ongoing study in the role of either site investigator, site coordinator or steering committee member.
Ashok Kakadekar
Lajos Kovacs
- Authors DF, BH, DH, MB, PH, LK, SL, KS, SS, AT and RW all provided significant contributions to the development of the study protocol in its development phase, and all are involved in this ongoing study in the role of either site investigator, site coordinator or steering committee member.
Shoo Lee
- Authors DF, BH, DH, MB, PH, LK, SL, KS, SS, AT and RW all provided significant contributions to the development of the study protocol in its development phase, and all are involved in this ongoing study in the role of either site investigator, site coordinator or steering committee member.
Koravangattu Sankaran
- Authors DF, BH, DH, MB, PH, LK, SL, KS, SS, AT and RW all provided significant contributions to the development of the study protocol in its development phase, and all are involved in this ongoing study in the role of either site investigator, site coordinator or steering committee member.
Stan Shapiro
- Authors DF, BH, DH, MB, PH, LK, SL, KS, SS, AT and RW all provided significant contributions to the development of the study protocol in its development phase, and all are involved in this ongoing study in the role of either site investigator, site coordinator or steering committee member.
John A. Smyth
Kuppuchipalayam Ramesh
Nicole Rouvinez Bouali
Alan Tinmouth
- Authors DF, BH, DH, MB, PH, LK, SL, KS, SS, AT and RW all provided significant contributions to the development of the study protocol in its development phase, and all are involved in this ongoing study in the role of either site investigator, site coordinator or steering committee member.
Robin Walker
- Authors DF, BH, DH, MB, PH, LK, SL, KS, SS, AT and RW all provided significant contributions to the development of the study protocol in its development phase, and all are involved in this ongoing study in the role of either site investigator, site coordinator or steering committee member.

Ottawa Health Research Institute, Ottawa, Ontario, Canada

The Ottawa Hospital, Faculty of Medicine, Ottawa, Ontario, Canada

McMaster University and Canadian Blood Services, Hamilton, Ontario, Canada

Children's and Women's Health Center of British Columbia, Vancouver, British Columbia, Canada

Royal University Hospital, Saskatoon, Saskatchewan, Canada

Jewish General Hospital, Montreal, Quebec, Canada

Capital Health, Edmonton, Alberta, Canada

McGill University Department of Epidemiology and Biostatistics, Montreal, Canada

Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada

IWK Health Center, Halifax, Nova Scotia, Canada

Despite recent trends in decreasing transfusion thresholds and the development of technologies designed to avoid allogeneic exposure, allogeneic red blood cell (RBC) transfusions remain an important supportive and life-saving measure for neonatal intensive care patients experiencing illness and anemia. Reluctantly, a number of laboratory and observational studies have indicated that the amount of time RBCs are stored can affect oxygen delivery to tissues. Consequently, older RBCs may result in higher rates of organ dysfunction, nosocomial infection, and lengths of stay. Because of such harmful effects, an evaluation of the association between age of blood and nosocomial infection and organ dysfunction is warranted. The aim of the study was to determine if RBCs stored for 7 days or less (fresh RBCs) compared to current standard transfusion practice decreases major nosocomial infection and organ dysfunction in neonates admitted to the neonatal intensive care unit and requiring at least one RBC transfusion. This study is a double-blind, multicenter, randomized controlled trial design. The trial will be an effectiveness study evaluating the effectiveness of stored vs fresh RBCs in neonates requiring transfusion. Neonatal patients requiring at least one unit of RBCs will be randomized to receive either (1) RBCs stored no longer than 7 days or (2) standard practice. The study was conducted in Canadian university-affiliated level III (tertiary) neonatal intensive care units. The primary outcome for this study will be a composite measure of major neonatal morbidities (necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage, and mortality). Secondary outcomes include individual items of the composite measure and nosocomial infection (bacteremia, septic shock, and pneumonia). The sample size calculations have been estimated based on the formula for 2 independent proportions using an α of .05, a (1-β) of .80, and a 10% noncompliance factor. The baseline rate for our composite measure is estimated to be 65% as indicated by the literature. Assuming a 15% absolute risk reduction with the use of RBCs stored 7 days or less, our estimated total sample size required will be 450 (225 patients per treatment arm). The Age of Red Blood Cells in Premature Infants (ARIPI) trial is registered at the US National Institutes of Health (ClinicalTrials.gov) no. NCT00326924 and current controlled trials ISRCTN65939658.