Randomized clinical trials

Project leaders: Anske van der Bom MD PhD and Prof Dick J van Rhenen MD PhD

The results of a RCT evaluating the efficacy of amatosalen pathogen-reduced platelet (PR) transfusions (HOVON 82; project leaders: DJ van Rhenen, A Brand) showed a decreased efficacy of PR-treated platelets. This led to the conclusion that implementation of this method for routine platelet preparation cannot be advised. It also initiated a new multicenter study evaluating PR using riboflavin (vitamin B2): the PREPAReS study.

The TRIGGER study

In 2010, the results of another RCT, the TRIGGER study; comparing a strict transfusion trigger with an operational hospital based trigger in orthopedic surgery, showed that the quality of life in the immediate postoperative period was not related to the patients’ hemoglobin level.

The TOMAAT study

In 2010 the final follow-up data of the TOMAAT study (Optimal blood management in orthopedic surgery) were completed. The final analysis of the study is in progress. Another study that ended in 2010 evaluated the effect of intravenous immunoglobulin (IVIG) to prevent exchange transfusions in hemolytic disease of the newborn due to Rh-antibodies. The study found no benefit of IVIG treatment.

Four RCTs were still ongoing in 2010 and two are in preparation.  A summary of the RCTs and their status at the end of 2010 is as follows:

The WOMB study

In the WOMB study (Well being of Obstetric patient on Minimal Blood transfusions, project leader: DJ van Rhenen) women with post-partum anemia are randomized to a restrictive and liberal transfusion trigger to compare post-partum fatigue and functioning. Rationale: approximately 3% of women receive one or more blood transfusions after clinical delivery. It is widely assumed that post-partum anemia leads to severe fatigue impairing breast-feeding and function. In the WOMB study, patients stratified for mode of delivery are randomized to a liberal and restrictive transfusion trigger and up to 6 weeks scored at regular intervals on validated QoL scales for fatigue and functioning. Additional support from the Landsteiner Foundation for Transfusion Research was obtained to complete the study. Inclusion of the 500 patients could be completed in early 2011.

The FIBER study

In the multicenter, semi-blinded, randomized FIBER (Fibrin Induced Blood Exposure Reduction study; project leaders: JA van Hilten, G Tavilla) study in CABG (coronary artery bypass graft) surgery the effect of Sanquin’s single donor plasma product fibrin sealant (Cryolijm) on reduction of transfusion needs and ICU stay is investigated. 1285 evaluable patients are required. By the end of 2010, 955 patients had been included in 7 centers.

The MATCH study

Cost-effectiveness of allo-immunization by pre-emptive extended (Rh, K, Fy-a, Jk-a, M & S) antigen-matching of red blood cell (RBC) transfusions is the primary outcome question of the MATCH study (project leaders: H Schonewille, A Brand). Alloimmunization against RBC antigens occurs in 1-10% of patients after a first transfusion event but, once immunized, 20-25% develops multiple RBC antibodies after subsequent transfusions. Identifying these patients before the first transfusion event is pivotal to define the target group for extended preventive matching. In the MATCH study, naive patients and patients who previously formed an antibody are stratified and randomized to either standard or extended matched RBC units. Of 1120 required patients, by the end of 2010, 415 patients have been included.

The PREPAReS study

The PREPAReS (Pathogen Reduction Evaluation & Predictive Analytical Rating Score study, project leaders: JA van Hilten, A Brand) is a non-inferiority, single blinded study to compare the clinical efficacy of the Mirasol (riboflavin/vitamin B2)-pathogen reduced platelet concentrates with standard platelet concentrates. The study started accrual end of November 2010 in the HAGA hospital (the Hague). Two other Dutch centers and centers in Norway and Canada intend contribution to the required intake of 618 patients.

The FIRST study

The FIRST (Fibrin Sealant in Total Knee Replacement surgery trial (project leaders: JA van Hilten, RGHH Nelissen) is a multi- or single donor Fibrin Sealant after total knee replacement surgery reduces post-surgical bleeding, swelling and pain. By the The Harris’ knee score as primary outcome postoperative knee function, estimated in flexion and extension at 2 and 6 weeks after surgery is evaluated. The study requires an intake of 500 evaluable patients. In the first week of 2011 inclusion started. The RBC-storage time study on clinical outcome in high risk intensive care patients (ABLE-NL, project leaders: LMG van de Watering, P Henny) is embedded in an international study (Canadian ABLE study). The presumed deleterious effect of stored RBC on clinical outcome was mainly evaluated in observational studies and a few pilot-RCTs. The correct interpretation of observational studies is crucial and we identified some most important pitfalls in these studies and identified conflicting outcomes. The national ABLE arm extends to medium risk ICU-patients.

Key publications