Prophylaxis of Thromboembolism in Critical Care (PROTECT) Trial: a pilot study.
OBJECTIVE
There is no randomized trial comparing low-molecular weight heparin (LMWH) and unfractionated heparin (UFH) for thromboprophylaxis in medical-surgical ICU patients. The primary objective of this randomized pilot study on LMWH vs UFH was to assess the feasibility of conducting a large randomized trial with respect to timely enrollment and blinded study drug administration, practicality of twice-weekly lower limb ultrasounds to screen for deep venous thrombosis, LMWH bioaccumulation and dose adjustment in renal insufficiency, and recruitment rates for a future trial in medical-surgical intensive care unit (ICU) patients. Its additional goals were to evaluate the suitability of the exclusion criteria and to document the range of research activities that precede accrual of patients into a trial to plan multisite management.


METHODS
By computerized telephone randomization, we allocated 129 medical-surgical ICU patients to treatment with dalteparin 5,000 IU QD SC or that with UFH 5,000 IU BID SC. Within each clinical center, only the study pharmacist was not blinded. We performed bilateral lower limb compression ultrasounds within 48 hours of ICU admission, twice weekly, on suspicion of deep venous thrombosis, and 7 days after ICU discharge. Research coordinators and investigators at 7 centers reported the time they engaged in all research activities before the first patient was randomized.


RESULTS
Timely complete study drug administration occurred after enrollment. More than 99% of scheduled doses were administered in a blinded fashion. Scheduled ultrasounds were performed without exception. No bioaccumulation of dalteparin was observed when creatinine clearance decreased to lower than 30 mL/min. Average recruitment was 2 patients/center per month before the study exclusion criteria were modified. Study startup activities required, on average, 65.5 hours of combined investigator and research coordinator time at each center. Careful examination of the accrual in the pilot study led to a reexamination of the Prophylaxis of Thromboembolism in Critical Care Trial (PROTECT) study exclusion criteria.


CONCLUSIONS
This pilot study suggests that a multicenter randomized clinical trial comparing LMWH with UFH in critically ill medical-surgical patients is feasible. Pilot studies can improve the design of larger trials and may enhance successful timely completion.
Cook
Deborah J
DJ
Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5. debcook@mcmaster.ca
Rocker
Graeme
G
Meade
Maureen
M
Guyatt
Gordon
G
Geerts
William
W
Anderson
David
D
Skrobik
Yoanna
Y
Hebert
Paul
P
Albert
Martin
M
Cooper
Jamie
J
Bates
Shannon
S
Caco
Christopher
C
Finfer
Simon
S
Fowler
Robert
R
Freitag
Andreas
A
Granton
John
J
Jones
Graham
G
Langevin
Stephan
S
Mehta
Sangeeta
S
Pagliarello
Giuseppe
G
Poirier
Germain
G
Rabbat
Christian
C
Schiff
David
D
Griffith
Lauren
L
Crowther
Mark
M
D000925:Anticoagulants / Q000627:therapeutic use*; D001315:Australia; D002170:Canada; D004311:Double-Blind Method; D005260:Female; D006493:Heparin / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D020246:Venous Thrombosis / Q000517:prevention & control*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin