Dataset Information

Recombinant factor VIIa concentrate versus plasma-derived concentrates for treating acute bleeding episodes in people with haemophilia and inhibitors.

ABSTRACT:

Background

In people with haemophilia, therapeutic clotting agents might be recognised as a foreign protein and induce anti-factor VIII antibodies, known as 'inhibitors'. Drugs insensitive to such antibodies, either recombinant or plasma-derived, are called factor VIII 'by-passing' agents and used for treatment of bleeding in people with inhibitors.

Objectives

To determine the clinical effectiveness of recombinant factor VIIa concentrate compared to plasma-derived concentrates for treating acute bleeding episodes in people with haemophilia and inhibitors.

Search methods

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Coagulopathies Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Coagulopathies Trials Register: 23 September 2015.

Selection criteria

Randomised and quasi-randomised controlled clinical trials comparing recombinant factor VIIa concentrate to human plasma-derived concentrates (high-dose human or recombinant factor VIII or factor IX concentrate; non-activated prothrombin complex concentrates; activated prothrombin complex concentrates) in people with haemophilia. Comparisons with animal-derived products were excluded.

Data collection and analysis

Two authors independently assessed the trials (eligibility and risk of bias) and extracted data. No combined meta-analyses were performed due to the unavailability of outcomes and comparisons common to the included trials.

Main results

A total of 15 trials were identified, two of which (with data for a total of 69 participants) were eligible for analysis. Both trials showed methodological flaws and did not show superiority of one treatment over the other. Both the treatments showed that recombinant factor VIIa and activated prothrombin complex concentrate appeared to have a similar haemostatic effect in both trials, without increasing thromboembolic risk.

Authors' conclusions

Based on the separate analysis of the two available randomised trials, recombinant factor VIIa and activated prothrombin complex concentrate were found to be similar in efficacy and safety. However, there is a need for further, well-designed, adequately-powered, randomised controlled trials to assess the relative benefits and risks of using recombinant factor VIIa compared to human plasma-derived concentrates in people with haemophilia with inhibitors. It is advisable that researchers in the field define commonly agreed objective outcome measures in order to enable the pooling of their results, thus increasing the power of comparisons. To date, data could not be combined in a formal meta-analysis. For the same reason reporting concordant and discordant pairs in cross-over trials is recommended.

SUBMITTER: Matino D

PROVIDER: S-EPMC7137678 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Hypofibrinogenaemia is associated with increased morbidity and mortality, but the optimal treatment level, the use of preemptive treatment and the preferred source of fibrinogen remain disputed. Fibrinogen concentrate is increasingly used and recommended for bleeding with acquired haemostatic deficiencies in several countries, but evidence is lacking regarding indications, dosing, efficacy and safety. OBJECTIVES:We assessed the benefits and harms of fibrinogen concentrate compared with placebo or usual treatment for bleeding patients. SEARCH METHODS:We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8); MEDLINE (1950 to 9 August 2013); EMBASE (1980 to 9 August 2013); International Web of Science (1964 to 9 August 2013); CINAHL (1980 to 9 August 2013); LILACS (1982 to 9 August 2013); and the Chinese Biomedical Literature Database (up to 10 November 2011), together with databases of ongoing trials. We contacted trial authors, authors of previous reviews and manufacturers in the field. SELECTION CRITERIA:We included all randomized controlled trials (RCTs), irrespective of blinding or language, that compared fibrinogen concentrate with placebo/other treatment or no treatment in bleeding patients, excluding neonates and patients with hereditary bleeding disorders. DATA COLLECTION AND ANALYSIS:Three review authors independently abstracted data; we resolved any disagreements by discussion. Our primary outcome measure was all-cause mortality. We performed subgroup and sensitivity analyses to assess the effects of fibrinogen concentrate in adults and children in terms of various clinical and physiological outcomes. We presented pooled estimates of the effects of intervention on dichotomous outcomes as risk ratios (RRs) and on continuous outcomes as mean differences, with 95% confidence intervals (CIs). We assessed the risk of bias through assessment of trial methodological components and the risk of random error through trial sequential analysis. MAIN RESULTS:We included six RCTs with a total of 248 participants; none of the trials were determined to have overall low risk of bias. We found 12 ongoing trials, from which we were unable to retrieve any data. Only two trials provided data on mortality, and one was a zero event study; thus the meta-analysis showed no statistically significant effect on overall mortality (2.6% vs 9.5%, RR 0.28, 95% CI 0.03 to 2.33). Our analyses on blood transfusion data suggest a beneficial effect of fibrinogen concentrate in reducing the incidence of allogenic transfusions (RR 0.47, 95% CI 0.31 to 0.72) but show no effect on other predefined outcomes, including adverse events such as thrombotic episodes. AUTHORS' CONCLUSIONS:In the six available RCTs of elective surgery, fibrinogen concentrate appears to reduce transfusion requirements, but the included trials are of low quality with high risk of bias and are underpowered to detect mortality, benefit or harm. Furthermore, data on mortality are lacking, heterogeneity is high and acute or severe bleeding in a non-elective surgical setting remains unexplored. Currently, weak evidence supports the use of fibrinogen concentrate in bleeding patients, as tested here in primarily elective cardiac surgery. More research is urgently needed.