Premature Infants in Need of Transfusion (PINT)

A Randomized Controlled Trial of Two Hemoglobin Thresholds for Transfusion in Newborns <1000g Birth Weight

Hypothesis: That a high hemoglobin threshold for transfusion in extremely low birth weight (ELBW) infants is associated with a lower rate of survival without severe morbidity (defined as one or more of retinopathy of prematurity, bronchopulmonary dysplasia, or periventricular leukomalacia/ventriculomegaly).

Primary Objective: To determine whether either a liberal or more restrictive threshold of hemoglobin level for red cell transfusion in ELBW infants is safer, by randomizing to either a high transfusion hemoglobin threshold or a low transfusion hemoglobin threshold.

Follow-up at a corrected age of 18 months represents a conventional age at which to first assess neurodevelopmental outcomes, and to predict long-term outcomes.

Study Overview

• Status: Completed
• Conditions: Anemia of Prematurity
• Intervention / Treatment: Procedure: Red blood cell transfusion

• Study Type: Interventional
• Enrollment: 424
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3084
      • Mercy Hospital for Women
    • Melbourne, Victoria, Australia, 3053
      • Royal Women's Hospital
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5H 3T9
      • Royal Alexandra Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3P 1R8
      • IWK Health Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4J9
      • McMaster University
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Hospital
    • Toronto, Ontario, Canada, M5S 1B2
      • Sunnybrook & Women's College Health Science Centre
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Royal Victoria Hospital
• United States
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • Brooklyn, New York, United States, 11201
      • Brooklyn Hospital Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• birth weight <1000g
• postnatal age <48 hours
• no transfusion beyond first 6 hours of life
• estimated gestational age of 30 completed weeks or less

Exclusion Criteria:

• infant considered non-viable by attending physician
• infant has cyanotic congenital heart disease
• infant's parents known to be opposed to blood transfusion
• either parent has hemoglobinopathies or congenital anemias
• infant has hemolytic disease
• infant has severe acute hemorrhage, severe shock, severe sepsis with coagulopathy or requires peri-operative transfusion
• prior treatment with or intention to treat with erythropoietin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Combined mortality or survival to tertiary hospital discharge without severe morbidity (BPD, severe ROP or brain injury)	neonatal phase
Combined mortality or survival with neurodevelopmental disability (non-ambulatory cerebral palsy, blindness, deafness, cognitive delay)	follow-up phase 18 months corrected age

Secondary Outcome Measures

Outcome Measure	Time Frame
growth in weight and head circumference	neonatal phase
time to extubation	neonatal phase
time on oxygen	neonatal phase
length of hospital stay until discharge home	neonatal phase
confirmed necrotizing enterocolitis	neonatal phase
apnea requiring treatment	neonatal phase
culture-proven infections	neonatal phase
use of post-natal steroids	neonatal phase
mean levels of hemoglobin	neonatal phase
number of transfusions	neonatal phase
number of donor exposures	neonatal phase
serum ferritin levels	neonatal phase
milder forms of cerebral palsy	follow-up phase 18 months corrected age
milder neurologic disorder	follow-up phase 18 months corrected age
personal and social functional capabilities	follow-up phase 18 months corrected age
hydrocephalus requiring a shunt	follow-up phase 18 months corrected age
seizure disorder	follow-up phase 18 months corrected age
respiratory disease	follow-up phase 18 months corrected age
iron nutritional status	follow-up phase 18 months corrected age
physical growth including head size	follow-up phase 18 months corrected age

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Haresh Kirpalani, MD, MSc, McMaster University; Principal Investigator: Robin K Whyte, MD, Dalhousie University; Study Director: Elizabeth Asztalos, MD, MSc, Sunnybrook & Women's College Health Sciences Centre; Study Director: Chad Andersen, MD, Mercy Hospital for Women; Study Director: Morris Blajchman, PhD, McMaster University; Study Director: Nancy Heddle, MSc, McMaster University

Publications and helpful links

General Publications

• Kirpalani H, Whyte RK, Andersen C, Asztalos EV, Heddle N, Blajchman MA, Peliowski A, Rios A, LaCorte M, Connelly R, Barrington K, Roberts RS. The Premature Infants in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants. J Pediatr. 2006 Sep;149(3):301-307. doi: 10.1016/j.jpeds.2006.05.011.
• Whyte RK, Kirpalani H, Asztalos EV, Andersen C, Blajchman M, Heddle N, LaCorte M, Robertson CM, Clarke MC, Vincer MJ, Doyle LW, Roberts RS; PINTOS Study Group. Neurodevelopmental outcome of extremely low birth weight infants randomly assigned to restrictive or liberal hemoglobin thresholds for blood transfusion. Pediatrics. 2009 Jan;123(1):207-13. doi: 10.1542/peds.2008-0338.

Study record dates

Study Major Dates

• Study Start: February 1, 2001
• Primary Completion (Actual): February 1, 2003
• Study Completion (Actual): November 1, 2005

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 16, 2005

Study Record Updates

• Last Update Posted (Estimate): September 24, 2015
• Last Update Submitted That Met QC Criteria: September 22, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: retinopathy of prematurity; bronchopulmonary dysplasia; periventricular leukomalacia; neonatal transfusion; ELBW premature infants; ventriculomegaly
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: CTMG-2001-PINT; CIHR MCT-41549; CIHR MCT-58455