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Meta-Analysis
. 2012 Mar 14;2012(3):CD004887.
doi: 10.1002/14651858.CD004887.pub3.

Human recombinant activated factor VII for upper gastrointestinal bleeding in patients with liver diseases

Arturo J Martí-Carvajal  1 , Despoina-Elvira Karakitsiou, Georgia Salanti
Affiliations
Meta-Analysis

Human recombinant activated factor VII for upper gastrointestinal bleeding in patients with liver diseases

Arturo J Martí-Carvajal et al. Cochrane Database Syst Rev. .

Abstract

Background: Mortality from upper gastrointestinal bleeding in patients with liver disease is high. Recombinant human activated factor VII (rHuFVIIa) has been suggested for patients with liver disease and upper gastrointestinal bleeding.

Objectives: To assess the beneficial and harmful effects of rHuFVIIa in patients with liver disease and upper gastrointestinal bleeding.

Search methods: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register (December 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 4, 2011), MEDLINE (1948 to December 2011), EMBASE (1980 to December 2011), Science Citation Index Expanded (1900 to December 2011), and LILACS (December 2011). We sought additional randomised trials from the reference lists of the trials and reviews identified through the electronic searches.

Selection criteria: Randomised clinical trials.

Data collection and analysis: Outcome data from randomised clinical trials were extracted and were presented using random-effects model meta-analyses. Data on the risk of bias in the included trials were also extracted.

Main results: We included two trials with 493 randomised participants with various Child-Pugh scores. The trials had a low risk of bias. The rHuFVIIa administration did not reduce the risk of mortality within five days (21/288 (7.3%) versus 15/205 (7.3%); risk ratio (RR) 0.88, 95% confidence interval (CI) 0.48 to 1.64, I(2) = 49%) and within 42 days (5/286 (1.7%) versus 36/205 (17.6%); RR 1.01, 95% CI 0.55 to 1.87, I(2) = 55%) when compared with placebo. Trial sequential analysis demonstrated that there is sufficient evidence to exclude that rHuFVIIa decreases mortality by 80%, but there is insufficient evidence to exclude smaller effects. The rHuFVIIa did not increase the risk of adverse events by number of patients (218/297 (74%) and 164/210 (78%); RR 0.94, 95% CI 0.84 to 1.04, I(2) = 1%), serious adverse events by adverse events reported (164/590 (28%) versus 123/443 (28%); RR 0.91, 95% CI 0.75 to 1.11, I(2) = 0%), and thromboembolic adverse events (16/297 (5.4%) versus 14/210 (6.7%); RR 0.80, 95% CI 0.40 to 1.60, I(2) = 0%) when compared with placebo.

Authors' conclusions: We found no evidence to support or reject the administration of rHuFVIIa for patients with liver disease and upper gastrointestinal bleeding. Further adequately powered randomised clinical trials are needed in order to evaluate the proper role of rHuFVIIa for treating upper gastrointestinal bleeding in patients with liver disease. Although the results are based on trials with low risk of bias, the heterogeneity and the small sample size result in rather large confidence intervals that cannot exclude the possibility that the intervention has some beneficial or harmful effect. Further trials with alow risk of bias are required to make more confident conclusions about the effects of the intervention.

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Conflict of interest statement

In 2004, Arturo Martí‐Carvajal was employed by Eli Lilly to run a four‐hour workshop on 'How to critically appraise clinical trials on osteoporosis and how to teach this'. This activity was not related to his work with The Cochrane Collaboration or any Cochrane review.

In 2007, Arturo Martí‐Carvajal was employed by Merck to run a four‐hour workshop 'How to critically appraise clinical trials and how to teach this'. This activity was not related to his work with The Cochrane Collaboration or any Cochrane review.

Georgia Salanti and Despoina‐Elvira Karakitsiou do not have any conflict of interest.

Figures

1
1
Flowchart of the search results (WHO: World Health Organization; CHBG: Cochrane Hepato‐Biliary Group; RCT: randomised controlled trial)
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
The heterogeneity‐corrected required information size (HCRIS) of 1830 patients has been calculated based upon a proportion of patients dying within five days of 7.3% in the control group; a relative risk reduction of 60% in the experimental intervention group; an alpha (α) of 5%; a beta (β) of 20%; and a diversity of 57%. The cumulative Z score does not reach the futility area (which is not even drawn by the program), demonstrating that if you want to introduce rHuFVIIa on the market with such an intervention effect, then further randomised trials are needed.
5
5
The heterogeneity‐corrected required information size (HCRIS) of 4668 patients has been calculated based upon a proportion of patients dying within five days of 7.3% in the control group; a RRR of 40% in the experimental intervention group; an alpha (α) of 5%; a beta (β) of 20%; and a diversity of 57%. The cumulative Z score does not reach the futility area (which is not even drawn by the program), demonstrating that if you want to introduce rHuFVIIa on the market with such an intervention effect, then further randomised trials are needed.
6
6
The heterogeneity‐corrected required information size (HCRIS) of 8784 patients has been calculated based upon a proportion of patients dying within five days of 7.3% in the control group; a RRR of 30% in the experimental intervention group; an alpha (α) of 5%; a beta (β) of 20%; and a diversity of 57%. The cumulative Z score does not reach the futility area (which is not even drawn by the program), demonstrating that if you want to introduce rHuFVIIa on the market with such an intervention effect, then further randomised trials are needed.
7
7
The heterogeneity‐corrected required information size (HCRIS) of 889 patients has been calculated based upon a proportion of patients dying within five days of 7.3% in the control group; a RRR of 80% in the experimental intervention group; an alpha (α) of 5%; a beta (β) of 20%; and a diversity of 57%. The cumulative Z score reaches the futility area (the two outward bending red curves), demonstrating that if you only want to introduce rHuFVIIa on the market with such large effect, then there is no need to conduct further trials.
1.1
1.1. Analysis
Comparison 1 Mortality (available cases analysis), Outcome 1 Deaths within 5 days.
1.2
1.2. Analysis
Comparison 1 Mortality (available cases analysis), Outcome 2 Deaths within 42 days.
2.1
2.1. Analysis
Comparison 2 Worst‐case scenario mortality, Outcome 1 Deaths within 5 days.
2.2
2.2. Analysis
Comparison 2 Worst‐case scenario mortality, Outcome 2 Deaths within 42 days.
3.1
3.1. Analysis
Comparison 3 Best‐case scenario mortality, Outcome 1 Deaths within 5 days.
3.2
3.2. Analysis
Comparison 3 Best‐case scenario mortality, Outcome 2 Deaths within 42 days.
4.1
4.1. Analysis
Comparison 4 Adverse events, Outcome 1 Overall incidence by patients.
4.2
4.2. Analysis
Comparison 4 Adverse events, Outcome 2 Serious adverse events by total adverse events.
4.3
4.3. Analysis
Comparison 4 Adverse events, Outcome 3 Thromboembolic adverse events by patients.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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References to other published versions of this review

Martí‐Carvajal 2007
    1. Marti‐Carvajal AJ, Salanti G, Marti‐Carvajal PI. Human recombinant activated factor VII for upper gastrointestinal bleeding in patients with liver diseases. Cochrane Database of Systematic Reviews 2007, Issue 1. [DOI: 10.1002/14651858.CD004887.pub2] - DOI - PubMed

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