Recombinant Activated Factor VII in the Management of Massive Bleeding in Hospital Universiti Sains Malaysia

Study Overview
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Brief Summary
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This is a retrospective descriptive study, to study the treatment indications, changes in transfusion need, coagulation profiles changes and clinical outcome (survival, complication) of non-haemophiliac patients who received activated factor seven (rFVIIa / NovoSeven®) during massive bleeding in Hospital Universiti Sains Malaysia (HUSM)

Detailed Description
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Effective hemostasis can be life-saving. However, there is still lack of an ideal hemostatic drug which is safe and effective. Recombinant activated factor VII (rFVIIa; Novo Nordisk, Bagsvaerd, Denmark) is a hemostatic agent originally developed for the management of bleeding in haemophilia A and B patients with inhibitors to factor VIII or IX respectively. Recombinant FVIIa involves in extrinsic clotting pathway where it forms a complex with tissue factor which in the presence of calcium and phospholipids activates coagulation factor X which then initiates the conversion of prothrombin into thrombin at the site of injury (Figure 1). Formation of thrombin and clot stabilises platelet plug and form a tight fibrin structure which is resistant to lysis. Due to the efficient haemostatic property but the unknown safety profile, it is only being used as one of the last resorts during massive intractable bleeding episode among the non-haemophilia patients. Efficacy and safety profile is the most important concern of a haemostatic drug like rFVIIa. However, there is ongoing controversial evidence regarding thromboembolic complications and survival benefit of the off-label use of rFVIIa in massive bleeding (Patel et al2012). This a study to learn about the previous usage, outcome and complications of rFVIIa use in massive intractable bleeding management in a single centre (Hospital University Sains Malaysia / HUSM) in Malaysia. The data of patients who had undergone massive bleeding will be available from pharmacy department and recruited from medical record department of HUSM. These include: Underlying condition, BMI of patient. Indication for blood transfusion. Dose of rFVIIa. Other medication (vitamin K, tranexamic acid, anticoagulant, antiplatelet) given to patient. Blood pressure, haemoglobin level, coagulation profile, and blood product requirements 24 hours before and after administration of rFVIIa. Survival at 24-hour and day-30 post administration of rFVIIa were also recorded. Thromboembolism complication post administration of rFVIIa. Duration of stay. Patients' identities will be anonymized without disclosure of personal identifiable information to third-party organizations. Statistical calculations will be done using SPSS (Statistical Package for the Social Science) software. Quantitative data will be expressed as mean ± standard deviation (SD) and median (interquartile range,IQR). For comparison before and after of administration of rFVIIa, data will be analyzed using paired t- test if the data is normally distributed. For skewed data, Wilcoxon Signed-Rank test will be used for analysis. The differences willl be considered significant at a p < 0.05. For the outcome of survival and thromboembolic complication, data will be analyzed descriptively with frequency and percentage.

Official Title
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Recombinant Activated Factor VII (rFVIIa/ NovoSeven®) in the Management of Massive Bleeding in Hospital Universiti Sains Malaysia

Conditions
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Massive Hemorrhage, Massive Blood Loss, Massive Blood Transfusion; Thrombocytopenia

Intervention / Treatment
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* Drug: NovoSeven


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patient with massive bleeding who had received rFVIIa from year 2006 to year 2016. Massive bleeding criteria Loss of one blood volume within a 24 hour 50% blood volume loss within 3 h Rate of loss of 150 ml/min Exclusion Criteria: Haemophilia patient who received rFVIIa Poor documentation / record unavailable in HUSM
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| NovoSeven<br>Non-hemophiliac patients experienced massive haemorrhage who was treated with recombinant activated factor VII | Drug: NovoSeven<br>* To survey retrospectively the treatment indications, clinical outcome, transfusion need and changes in coagulation profiles of non-haemophiliac patients who had received rFVIIa during massive bleeding<br>* Other names: recombinant activated factor VII;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in blood transfusion requirement | To study the changes in blood product requirement in 24 hours before and after administration of rFVIIa in massive bleeding patient in HUSM and to describe the factors affecting it. | 24 hour before and after administration of rFVIIa | 
| Survival rate | To describe the outcome of survival at 24-hour and Day-30 after receiving rFVIIa | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in coagulation profile | To study the changes in coagulation profile in 24 hours before and after administration of rFVIIa in massive bleeding patient in HUSM and to describe the factors affecting it | 24 hour before and after administration of rFVIIa | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rFVIIa, Massive Hemorrhage, non-hemophilia