Recombinant activated factor VII safety in trauma patients: results from the CONTROL trial.

Abstract

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.

• Authors: Richard P Dutton, Michael Parr, Bartholomew J Tortella, Howard R Champion, Gordon R Bernard, Kenneth Boffard, Bertil Bouillon, Martin A Croce, Jeannett Dimsits, John B Holcomb, Ari Leppaniemi, Jean-Louis Vincent, Carl J Hauser, CONTROL Study Group
• Journal: The Journal of trauma (J Trauma) Vol. 71 Issue 1 Pg. 12-9 (Jul 2011) ISSN: 1529-8809 [Electronic] United States
• PMID: 21610529 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• recombinant FVIIa
• Factor VIIa

Topics

• Europe (epidemiology)
• Factor VIIa (administration & dosage, therapeutic use)
• Follow-Up Studies
• Humans
• Incidence
• Multiple Organ Failure (epidemiology, etiology, prevention & control)
• Myocardial Infarction (complications, epidemiology, prevention & control)
• Recombinant Proteins (administration & dosage, therapeutic use)
• Respiratory Distress Syndrome (complications, epidemiology, prevention & control)
• Risk Factors
• Survival Rate
• Thoracic Injuries (complications, diagnosis)
• Thromboembolism (diagnosis, drug therapy, epidemiology)
• Trauma Severity Indices
• Treatment Outcome
• United States (epidemiology)