Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2011

Open Access 01-12-2011 | Study protocol

Transfusion of fresh frozen plasma in non-bleeding ICU patients -TOPIC TRIAL: study protocol for a randomized controlled trial

Authors: Marcella CA Müller, Evert de Jonge, M Sesmu Arbous, Angelique ME Spoelstra -de Man, Atilla Karakus, Margreeth B Vroom, Nicole P Juffermans

Published in: Trials | Issue 1/2011

Login to get access

Abstract

Background

Fresh frozen plasma (FFP) is an effective therapy to correct for a deficiency of multiple coagulation factors during bleeding. In past years, use of FFP has increased, in particular in patients on the Intensive Care Unit (ICU), and has expanded to include prophylactic use in patients with a coagulopathy prior to undergoing an invasive procedure. Retrospective studies suggest that prophylactic use of FFP does not prevent bleeding, but carries the risk of transfusion-related morbidity. However, up to 50% of FFP is administered to non-bleeding ICU patients. With the aim to investigate whether prophylactic FFP transfusions to critically ill patients can be safely omitted, a multi-center randomized clinical trial is conducted in ICU patients with a coagulopathy undergoing an invasive procedure.

Methods

A non-inferiority, prospective, multicenter randomized open-label, blinded end point evaluation (PROBE) trial. In the intervention group, a prophylactic transfusion of FFP prior to an invasive procedure is omitted compared to transfusion of a fixed dose of 12 ml/kg in the control group. Primary outcome measure is relevant bleeding. Secondary outcome measures are minor bleeding, correction of International Normalized Ratio, onset of acute lung injury, length of ventilation days and length of Intensive Care Unit stay.

Discussion

The Transfusion of Fresh Frozen Plasma in non-bleeding ICU patients (TOPIC) trial is the first multi-center randomized controlled trial powered to investigate whether it is safe to withhold FFP transfusion to coagulopathic critically ill patients undergoing an invasive procedure.

Trial Registration

Trial registration: Dutch Trial Register NTR2262 and ClinicalTrials.gov: NCT01143909
Appendix
Available only for authorised users
Literature
1.
Chowdhury P, Saayman AG, Paulus U, Findlay GP, Collins PW: Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol. 2004, 125: 69-73. 10.1111/j.1365-2141.2004.04868.x.CrossRefPubMed
2.
3.
O'Shaughnessy DF, Atterbury C, Bolton MP, Murphy M, Thomas D, Yates S, Williamson LM: Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Haematol. 2004, 126: 11-28.CrossRefPubMed
4.
Wallis JP, Dzik S: Is fresh frozen plasma overtransfused in the United States?. Transfusion. 2004, 44: 1674-1675. 10.1111/j.0041-1132.2004.00427.x.CrossRefPubMed
5.
Stanworth SJ, Brunskill SJ, Hyde CJ, McClelland DB, Murphy MF: Is fresh frozen plasma clinically effective? A systematic review of randomized controlled trials. Br J Haematol. 2004, 126: 139-152. 10.1111/j.1365-2141.2004.04973.x.CrossRefPubMed
6.
Holland L, Sarode R: Should plasma be transfused prophylactically before invasive procedures?. Curr Opin Hematol. 2006, 13: 447-451. 10.1097/01.moh.0000245688.47333.b6.CrossRefPubMed
7.
Dara SI, Rana R, Afessa B, Moore SB, Gajic O: Fresh frozen plasma transfusion in critically ill medical patients with coagulopathy. Crit Care Med. 2005, 33: 2667-2671. 10.1097/01.CCM.0000186745.53059.F0.CrossRefPubMed
8.
Gajic O, Rana R, Winters JL, Yilmaz M, Mendez JL, Rickman OB, O'Byrne MM, Evenson LK, Malinchoc M, DeGoey SR, Afessa B, Hubmayr RD, Moore SB: Transfusion-related acute lung injury in the critically ill: prospective nested case-control study. Am J Respir Crit Care Med. 2007, 176: 886-891. 10.1164/rccm.200702-271OC.CrossRefPubMedPubMedCentral
9.
Vlaar AP, Binnekade JM, Prins D, van SD, Hofstra JJ, Schultz MJ, Juffermans NP: Risk factors and outcome of transfusion-related acute lung injury in the critically ill: a nested case-control study. Crit Care Med. 2010, 38: 771-778. 10.1097/CCM.0b013e3181cc4d4b.CrossRefPubMed
10.
Vlaar AP, in der Maur AL, Binnekade JM, Schultz MJ, Juffermans NP: A survey of physicians' reasons to transfuse plasma and platelets in the critically ill: a prospective single-centre cohort study. Transfus Med. 2009, 19: 207-212. 10.1111/j.1365-3148.2009.00928.x.CrossRefPubMed
11.
Dzik W, Rao A: Why do physicians request fresh frozen plasma?. Transfusion. 2004, 44: 1393-1394. 10.1111/j.0041-1132.2004.00422.x.CrossRefPubMed
12.
Watson DM, Stanworth SJ, Wyncoll D, McAuley DF, Perkins GD, Young D, Biggin KJ, Walsh TS: A national clinical scenario-based survey of clinicians' attitudes towards fresh frozen plasma transfusion for critically ill patients. Transfus Med. 2011, 21: 124-129. 10.1111/j.1365-3148.2010.01049.x.CrossRefPubMed
13.
Walsh TS, Stanworth SJ, Prescott RJ, Lee RJ, Watson DM, Wyncoll D: Prevalence, management, and outcomes of critically ill patients with prothrombin time prolongation in United Kingdom intensive care units. Crit Care Med. 2010, 38: 1939-1946.CrossRefPubMed
14.
Arnold DM, Donahoe L, Clarke FJ, Tkaczyk AJ, Heels-Ansdell D, Zytaruk N, Cook R, Webert KE, McDonald E, Cook DJ: Bleeding during critical illness: a prospective cohort study using a new measurement tool. Clin Invest Med. 2007, 30: E93-102.PubMed
15.
Murray JF, Matthay MA, Luce JM, Flick MR: An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis. 1988, 138: 720-723.CrossRefPubMed
16.
Zimmerman JE, Kramer AA, McNair DS, Malila FM: Acute Physiology and Chronic Health Evaluation (APACHE) IV: hospital mortality assessment for today's critically ill patients. Crit Care Med. 2006, 34: 1297-1310. 10.1097/01.CCM.0000215112.84523.F0.CrossRefPubMed
17.
Al DA, Haddad S, Arabi Y, Dabbagh O, Cook DJ: The safety of percutaneous tracheostomy in patients with coagulopathy or thrombocytopenia. Middle East J Anesthesiol. 2007, 19: 37-49.
18.
Auzinger G, O'Callaghan GP, Bernal W, Sizer E, Wendon JA: Percutaneous tracheostomy in patients with severe liver disease and a high incidence of refractory coagulopathy: a prospective trial. Crit Care. 2007, 11: R110-10.1186/cc6143.CrossRefPubMedPubMedCentral
19.
Doerfler ME, Kaufman B, Goldenberg AS: Central venous catheter placement in patients with disorders of hemostasis. Chest. 1996, 110: 185-188. 10.1378/chest.110.1.185.CrossRefPubMed
20.
Fisher NC, Mutimer DJ: Central venous cannulation in patients with liver disease and coagulopathy--a prospective audit. Intensive Care Med. 1999, 25: 481-485. 10.1007/s001340050884.CrossRefPubMed
21.
Foster PF, Moore LR, Sankary HN, Hart ME, Ashmann MK, Williams JW: Central venous catheterization in patients with coagulopathy. Arch Surg. 1992, 127: 273-275. 10.1001/archsurg.1992.01420030035006.CrossRefPubMed
22.
Goldfarb G, Lebrec D: Percutaneous cannulation of the internal jugular vein in patients with coagulopathies: an experience based on 1,000 attempts. Anesthesiology. 1982, 56: 321-323. 10.1097/00000542-198204000-00021.CrossRefPubMed
23.
Kluge S, Meyer A, Kuhnelt P, Baumann HJ, Kreymann G: Percutaneous tracheostomy is safe in patients with severe thrombocytopenia. Chest. 2004, 126: 547-551. 10.1378/chest.126.2.547.CrossRefPubMed
24.
Pandit RA, Jacques TC: Audit of over 500 percutaneous dilational tracheostomies. Crit Care Resusc. 2006, 8: 146-150.PubMed
25.
Talving P, Benfield R, Hadjizacharia P, Inaba K, Chan LS, Demetriades D: Coagulopathy in severe traumatic brain injury: a prospective study. J Trauma. 2009, 66: 55-61. 10.1097/TA.0b013e318190c3c0.CrossRefPubMed
26.
Levi M, Meijers JC: DIC: which laboratory tests are most useful. Blood Rev. 2011, 25: 33-37. 10.1016/j.blre.2010.09.002.CrossRefPubMed
27.
Mumtaz H, Williams V, Hauer-Jensen M, Rowe M, Henry-Tillman RS, Heaton K, Mancino AT, Muldoon RL, Klimberg VS, Broadwater JR, Westbrook KC, Lang NP: Central venous catheter placement in patients with disorders of hemostasis. Am J Surg. 2000, 180: 503-505. 10.1016/S0002-9610(00)00552-3.CrossRefPubMed
28.
Rosseland LA, Laake JH, Stubhaug A: Percutaneous dilatational tracheotomy in intensive care unit patients with increased bleeding risk or obesity. A prospective analysis of 1000 procedures. Acta Anaesthesiol Scand. 2011, 55: 835-841. 10.1111/j.1399-6576.2011.02458.x.CrossRefPubMed
29.
McVay PA, Toy PT: Lack of increased bleeding after paracentesis and thoracentesis in patients with mild coagulation abnormalities. Transfusion. 1991, 31: 164-171. 10.1046/j.1537-2995.1991.31291142949.x.CrossRefPubMed
30.
Iorio A, Basileo M, Marchesini E, Materazzi M, Marchesi M, Esposito A, Palazzesi GP, Pellegrini L, Pasqua BL, Rocchetti L, Silvani CM: The good use of plasma. A critical analysis of five international guidelines. Blood Transfus. 2008, 6: 18-24.PubMedPubMedCentral
31.
Stanworth SJ, Grant-Casey J, Lowe D, Laffan M, New H, Murphy MF, Allard S: The use of fresh-frozen plasma in England: high levels of inappropriate use in adults and children. Transfusion. 2011, 51: 62-70. 10.1111/j.1537-2995.2010.02798.x.CrossRefPubMed
32.
Stanworth SJ, Walsh TS, Prescott RJ, Lee RJ, Watson DM, Wyncoll D: A national study of plasma use in critical care: clinical indications, dose and effect on prothrombin time. Crit Care. 2011, 15: R108-10.1186/cc10129.CrossRefPubMedPubMedCentral
33.
Veelo DP, Dongelmans DA, Phoa KN, Spronk PE, Schultz MJ: Tracheostomy: current practice on timing, correction of coagulation disorders and peri-operative management - a postal survey in the Netherlands. Acta Anaesthesiol Scand. 2007, 51: 1231-1236. 10.1111/j.1399-6576.2007.01430.x.CrossRefPubMed
34.
Lauzier F, Cook D, Griffith L, Upton J, Crowther M: Fresh frozen plasma transfusion in critically ill patients. Crit Care Med. 2007, 35: 1655-1659. 10.1097/01.CCM.0000269370.59214.97.CrossRefPubMed
35.
Tinmouth A, Chatelain E, Fergusson D, McIntyre L, Giulivi A, Hebert P: A Randomized Controlled Trial of High and Standard Dose Fresh Frozen Plasma Transfusions in Critically Ill Patients. Transfusion. 2008, 48: 26A-27A.
36.
Abdel-Wahab OI, Healy B, Dzik WH: Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities. Transfusion. 2006, 46: 1279-1285. 10.1111/j.1537-2995.2006.00891.x.CrossRefPubMed
37.
Holland LL, Foster TM, Marlar RA, Brooks JP: Fresh frozen plasma is ineffective for correcting minimally elevated international normalized ratios. Transfusion. 2005, 45: 1234-1235. 10.1111/j.1537-2995.2005.00184.x.CrossRefPubMed
38.
Holland LL, Brooks JP: Toward rational fresh frozen plasma transfusion: The effect of plasma transfusion on coagulation test results. Am J Clin Pathol. 2006, 126: 133-139. 10.1309/NQXHUG7HND78LFFK.CrossRefPubMed
39.
Gajic O, Dara SI, Mendez JL, Adesanya AO, Festic E, Caples SM, Rana R, St Sauver JL, Lymp JF, Afessa B, Hubmayr RD: Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med. 2004, 32: 1817-1824. 10.1097/01.CCM.0000133019.52531.30.CrossRefPubMed
40.
Khan H, Belsher J, Yilmaz M, Afessa B, Winters JL, Moore SB, Hubmayr RD, Gajic O: Fresh-frozen plasma and platelet transfusions are associated with development of acute lung injury in critically ill medical patients. Chest. 2007, 131: 1308-1314. 10.1378/chest.06-3048.CrossRefPubMed
41.
Gajic O, Dzik WH, Toy P: Fresh frozen plasma and platelet transfusion for nonbleeding patients in the intensive care unit: benefit or harm?. Crit Care Med. 2006, 34: S170-S173. 10.1097/01.CCM.0000214288.88308.26.CrossRefPubMed
42.
Gajic O, Yilmaz M, Iscimen R, Kor DJ, Winters JL, Moore SB, Afessa B: Transfusion from male-only versus female donors in critically ill recipients of high plasma volume components. Crit Care Med. 2007, 35: 1645-1648. 10.1097/01.CCM.0000269036.16398.0D.CrossRefPubMed
43.
Wright SE, Snowden CP, Athey SC, Leaver AA, Clarkson JM, Chapman CE, Roberts DR, Wallis JP: Acute lung injury after ruptured abdominal aortic aneurysm repair: the effect of excluding donations from females from the production of fresh frozen plasma. Crit Care Med. 2008, 36: 1796-1802. 10.1097/CCM.0b013e3181743c6e.CrossRefPubMed
44.
Rana R, Fernandez-Perez ER, Khan SA, Rana S, Winters JL, Lesnick TG, Moore SB, Gajic O: Transfusion-related acute lung injury and pulmonary edema in critically ill patients: a retrospective study. Transfusion. 2006, 46: 1478-1483. 10.1111/j.1537-2995.2006.00930.x.CrossRefPubMed
45.
Jia X, Malhotra A, Saeed M, Mark RG, Talmor D: Risk factors for ARDS in patients receiving mechanical ventilation for > 48 h. Chest. 2008, 133: 853-861. 10.1378/chest.07-1121.CrossRefPubMed
46.
Gajic O, Rana R, Mendez JL, Rickman OB, Lymp JF, Hubmayr RD, Moore SB: Acute lung injury after blood transfusion in mechanically ventilated patients. Transfusion. 2004, 44: 1468-1474. 10.1111/j.1537-2995.2004.04053.x.CrossRefPubMed
47.
Hansson L, Hedner T, Dahlof B: Prospective randomized open blinded end-point (PROBE) study. A novel design for intervention trials. Prospective Randomized Open Blinded End-Point. Blood Press. 1992, 1: 113-119. 10.3109/08037059209077502.CrossRefPubMed
48.
Smith DH, Neutel JM, Lacourciere Y, Kempthorne-Rawson J: Prospective, randomized, open-label, blinded-endpoint (PROBE) designed trials yield the same results as double-blind, placebo-controlled trials with respect to ABPM measurements. J Hypertens. 2003, 21: 1291-1298. 10.1097/00004872-200307000-00016.CrossRefPubMed
Metadata
Title
Transfusion of fresh frozen plasma in non-bleeding ICU patients -TOPIC TRIAL: study protocol for a randomized controlled trial
Authors
Marcella CA Müller
Evert de Jonge
M Sesmu Arbous
Angelique ME Spoelstra -de Man
Atilla Karakus
Margreeth B Vroom
Nicole P Juffermans
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Trials / Issue 1/2011
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/1745-6215-12-266

Other articles of this Issue 1/2011

Trials 1/2011 Go to the issue

Study protocol

Vocational rehabilitation services for patients with cancer: design of a feasibility study incorporating a pilot randomised controlled trial among women with breast cancer following surgery

Research

Effects on patients of their healthcare practitioner's or institution's participation in clinical trials: a systematic review

Research

Standard requirements for GCP-compliant data management in multinational clinical trials

Study protocol

Pancreatitis, very early compared with normal start of enteral feeding (PYTHON trial): design and rationale of a randomised controlled multicenter trial

Methodology

Pre-referral rectal artesunate in severe malaria: flawed trial

Study protocol

A randomised controlled trial to compare opt-in and opt-out parental consent for childhood vaccine safety surveillance using data linkage: study protocol