TY - JOUR
T1 - Recombinant activated factor VII safety in trauma patients
T2 - results from the CONTROL trial
AU - Dutton, Richard P.
AU - Parr, Michael
AU - Tortella, Bartholomew J.
AU - Champion, Howard R.
AU - Bernard, Gordon R.
AU - Boffard, Kenneth
AU - Bouillon, Bertil
AU - Croce, Martin A.
AU - Dimsits, Jeannett
AU - Holcomb, John B.
AU - Leppaniemi, Ari
AU - Vincent, Jean-Louis
AU - Hauser, Carl J.
PY - 2011/7/1
Y1 - 2011/7/1
N2 - Background: Safety data on recombinant activated factor VII (rFVIIa, NovoSeven; Novo Nordisk A/S, Bagsværd, Denmark) in actively hemorrhaging trauma patients are limited. We present detailed safety data from a large multicenter, randomized, placebo-controlled phase III study (the CONTROL trial). Methods: Data from 560 patients were analyzed. Subjects were monitored for adverse events (AEs) after rFVIIa or placebo administration. Incidences, timing, and presence of risk factors were reported by site investigators, supported by external study monitors and overseen by an independent Data Monitoring Committee. Results: There were no differences in overall mortality, organ system failure, or AEs, serious AEs, or medical events of special interest. Arterial and venous thromboembolic (TE) events and their risk factors were similar in both groups. The greatest risk factor for TE events was a chest injury requiring mechanical ventilation >3 days (86%). There were four site investigator-reported myocardial infarctions in the rFVIIa group of which only one met diagnostic criteria preestablished by the Data Monitoring Committee. There were no reported myocardial infarctions in the placebo group. Troponins were increased in 30% of all patients. The rate of acute respiratory distress syndrome was lower in the rFVIIa (3.0%) than in the placebo (7.2%) group (p = 0.022). Conclusions: This represents the largest placebo-controlled dataset of rFVIIa use in trauma patients to date. In this prospective study of critically bleeding trauma patients, rFVIIa use was associated with an imbalance of investigator-reported Acute myocardial infarction/non-ST segment elevation myocardial infarction (AMI/NSTEMI), but was not associated with an increased risk for other AEs, including TE complications.
AB - Background: Safety data on recombinant activated factor VII (rFVIIa, NovoSeven; Novo Nordisk A/S, Bagsværd, Denmark) in actively hemorrhaging trauma patients are limited. We present detailed safety data from a large multicenter, randomized, placebo-controlled phase III study (the CONTROL trial). Methods: Data from 560 patients were analyzed. Subjects were monitored for adverse events (AEs) after rFVIIa or placebo administration. Incidences, timing, and presence of risk factors were reported by site investigators, supported by external study monitors and overseen by an independent Data Monitoring Committee. Results: There were no differences in overall mortality, organ system failure, or AEs, serious AEs, or medical events of special interest. Arterial and venous thromboembolic (TE) events and their risk factors were similar in both groups. The greatest risk factor for TE events was a chest injury requiring mechanical ventilation >3 days (86%). There were four site investigator-reported myocardial infarctions in the rFVIIa group of which only one met diagnostic criteria preestablished by the Data Monitoring Committee. There were no reported myocardial infarctions in the placebo group. Troponins were increased in 30% of all patients. The rate of acute respiratory distress syndrome was lower in the rFVIIa (3.0%) than in the placebo (7.2%) group (p = 0.022). Conclusions: This represents the largest placebo-controlled dataset of rFVIIa use in trauma patients to date. In this prospective study of critically bleeding trauma patients, rFVIIa use was associated with an imbalance of investigator-reported Acute myocardial infarction/non-ST segment elevation myocardial infarction (AMI/NSTEMI), but was not associated with an increased risk for other AEs, including TE complications.
KW - Hemorrhage
KW - Recombinant factor VIIa
KW - Safety
KW - Thromboembolic complications
KW - Trauma
UR - http://www.scopus.com/inward/record.url?scp=79960390714&partnerID=8YFLogxK
U2 - 10.1097/TA.0b013e31821a42cf
DO - 10.1097/TA.0b013e31821a42cf
M3 - Article
VL - 71
SP - 12
EP - 18
JO - Journal of Trauma - Injury, Infection and Critical Care
JF - Journal of Trauma - Injury, Infection and Critical Care
SN - 1079-6061
IS - 1
ER -