Massive HemorrhageNCT03251547
Recombinant Activated Factor VII in the Management of Massive Bleeding in Hospital Universiti Sains Malaysia
An observational study of Massive Hemorrhage and Massive Blood Loss, run by Universiti Sains Malaysia at 1 site in Malaysia.
Trial summary
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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Massive Hemorrhage, Massive Blood Loss, Massive Blood Transfusion; Thrombocytopenia
- What is being tested?
- NovoSeven
- How many people
- 76 participants
- Where
- 1 siteMalaysia
- Study dates
- 21 Aug 2017to 15 Nov 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Non-haemophilic patients who had received rFVIIa during massive bleeding in Hospital Universiti Sains Malaysia (HUSM)
Who may be able to join
- 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
Who cannot join
- Haemophilia patient who received rFVIIa
- Poor documentation / record unavailable in HUSM
Trial locations and contacts
1 site in 1 country.
Malaysia1 site
Hospital Universiti Sains Malaysia
Kota Bharu, Kelantan, 16150
About this study
Official title: Recombinant Activated Factor VII (rFVIIa/ NovoSeven®) in the Management of Massive Bleeding in Hospital Universiti Sains Malaysia
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)
Read the detailed description
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.
- Being tested
- NovoSeven
- Keywords
- rFVIIa, Massive Hemorrhage, non-hemophilia
- Medical subject headings
- Thrombocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NovoSevenDrug
Also called recombinant activated factor VII
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
| Study group | Role | What they receive |
|---|---|---|
| NovoSeven | Non-hemophiliac patients experienced massive haemorrhage who was treated with recombinant activated factor VII Receives: Drug: NovoSeven |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 30 days
Secondary outcomes (1)
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
Measured: 24 hour before and after administration of rFVIIa
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2017
- Study start21 Aug 2017
- Primary completion15 Oct 2017
- Study completion15 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Massive HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universiti Sains Malaysia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Soon Eu Chong, Universiti Sains Malaysia
- Investigators
- Chong Soon Eu, MD, MMed, Study chair, Universiti Sains MalaysiaNurfatin Mohd Shah, BSc, Principal investigator, Universiti Sains Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03251547
- Sponsor's protocol ID
- SEChong
- Status last verified
- Oct 2018
- First submitted
- 11 Aug 2017
- Last updated
- 10 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Hunt BJ. Bleeding and coagulopathies in critical care. N Engl J Med. 2014 Feb 27;370(9):847-59. doi: 10.1056/NEJMra1208626. No abstract available.
PubMed 24571757Bougle A, Harrois A, Duranteau J. Resuscitative strategies in traumatic hemorrhagic shock. Ann Intensive Care. 2013 Jan 12;3(1):1. doi: 10.1186/2110-5820-3-1.
PubMed 23311726Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M, Burch JM, Galloway B. Predicting life-threatening coagulopathy in the massively transfused trauma patient: hypothermia and acidoses revisited. J Trauma. 1997 May;42(5):857-61; discussion 861-2. doi: 10.1097/00005373-199705000-00016.
PubMed 9191667Faraoni D, Van Der Linden P. A systematic review of antifibrinolytics and massive injury. Minerva Anestesiol. 2014 Oct;80(10):1115-22. Epub 2013 Nov 28.
PubMed 24287671Franchini M. The use of desmopressin as a hemostatic agent: a concise review. Am J Hematol. 2007 Aug;82(8):731-5. doi: 10.1002/ajh.20940.
PubMed 17492648Kobayashi T, Nakabayashi M, Yoshioka A, Maeda M, Ikenoue T. Recombinant activated factor VII (rFVIIa/NovoSeven(R)) in the management of severe postpartum haemorrhage: initial report of a multicentre case series in Japan. Int J Hematol. 2012 Jan;95(1):57-63. doi: 10.1007/s12185-011-0974-9. Epub 2011 Dec 9.
PubMed 22160834Lin Y, Moltzan CJ, Anderson DR; National Advisory Committee on Blood and Blood Products. The evidence for the use of recombinant factor VIIa in massive bleeding: revision of the transfusion policy framework. Transfus Med. 2012 Dec;22(6):383-94. doi: 10.1111/j.1365-3148.2012.01164.x. Epub 2012 May 27.
PubMed 22630348Logan AC, Goodnough LT. Recombinant factor VIIa: an assessment of evidence regarding its efficacy and safety in the off-label setting. Hematology Am Soc Hematol Educ Program. 2010;2010:153-9. doi: 10.1182/asheducation-2010.1.153.
PubMed 21239786Palmason R, Vidarsson B, Sigvaldason K, Ingimarsson JP, Gudbjartsson T, Sigurdsson GH, Onundarson PT. Recombinant factor VIIa as last-resort treatment of desperate haemorrhage. Acta Anaesthesiol Scand. 2012 May;56(5):636-44. doi: 10.1111/j.1399-6576.2012.02688.x.
PubMed 22489992Spahn DR, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Filipescu D, Hunt BJ, Komadina R, Nardi G, Neugebauer E, Ozier Y, Riddez L, Schultz A, Vincent JL, Rossaint R. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care. 2013 Apr 19;17(2):R76. doi: 10.1186/cc12685.
PubMed 23601765Stainsby D, MacLennan S, Hamilton PJ. Management of massive blood loss: a template guideline. Br J Anaesth. 2000 Sep;85(3):487-91. doi: 10.1093/bja/85.3.487.
PubMed 11103199Yank V, Tuohy CV, Logan AC, Bravata DM, Staudenmayer K, Eisenhut R, Sundaram V, McMahon D, Olkin I, McDonald KM, Owens DK, Stafford RS. Systematic review: benefits and harms of in-hospital use of recombinant factor VIIa for off-label indications. Ann Intern Med. 2011 Apr 19;154(8):529-40. doi: 10.7326/0003-4819-154-8-201104190-00004.
PubMed 21502651
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Recombinant Activated Factor VII (rFVIIa/ NovoSeven®) in the Management of Massive Bleeding in Hospital Universiti Sains Malaysia
- ClinicalTrials.gov ID
- NCT03251547
- Acronym / sponsor ID
- SEChong
- Keywords
- rFVIIa, Massive Hemorrhage, non-hemophilia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Universiti Sains MalaysiaUniversity, hospital or other
- Study start
- 21 Aug 2017 (actual)
- Primary completion
- 15 Oct 2017 (actual)
- Study completion
- 15 Nov 2017 (actual)
- First posted
- 16 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NovoSeven | – | Drug: NovoSevenNon-hemophiliac patients experienced massive haemorrhage who was treated with recombinant activated factor VII |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Non-haemophilic patients who had received rFVIIa during massive bleeding in Hospital Universiti Sains Malaysia (HUSM)
Key inclusion criteria (5 listed)
- All patient with massive bleeding who had received rFVIIa from year 2006 to year 2016.
- Massive bleeding criteria
Key exclusion criteria (2 listed)
- Haemophilia patient who received rFVIIa
- Poor documentation / record unavailable in HUSM
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NovoSevenAlso: recombinant activated factor VIITo 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 | Drug | NovoSeven |
Primary outcome
Changes in blood transfusion requirement
Time frame: 24 hour before and after administration of rFVIIa
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.
Survival rate
Time frame: 30 days
To describe the outcome of survival at 24-hour and Day-30 after receiving rFVIIa
1 secondary outcome
Changes in coagulation profile
Time frame: 24 hour before and after administration of rFVIIa
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2018.
- Background: PubMed 24571757Hunt BJ. Bleeding and coagulopathies in critical care. N Engl J Med. 2014 Feb 27;370(9):847-59. doi: 10.1056/NEJMra1208626. No abstract available.
- Background: PubMed 23311726Bougle A, Harrois A, Duranteau J. Resuscitative strategies in traumatic hemorrhagic shock. Ann Intensive Care. 2013 Jan 12;3(1):1. doi: 10.1186/2110-5820-3-1.
- Background: PubMed 9191667Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M, Burch JM, Galloway B. Predicting life-threatening coagulopathy in the massively transfused trauma patient: hypothermia and acidoses revisited. J Trauma. 1997 May;42(5):857-61; discussion 861-2. doi: 10.1097/00005373-199705000-00016.
- Background: PubMed 24287671Faraoni D, Van Der Linden P. A systematic review of antifibrinolytics and massive injury. Minerva Anestesiol. 2014 Oct;80(10):1115-22. Epub 2013 Nov 28.
- Background: PubMed 17492648Franchini M. The use of desmopressin as a hemostatic agent: a concise review. Am J Hematol. 2007 Aug;82(8):731-5. doi: 10.1002/ajh.20940.
- Background: PubMed 22160834Kobayashi T, Nakabayashi M, Yoshioka A, Maeda M, Ikenoue T. Recombinant activated factor VII (rFVIIa/NovoSeven(R)) in the management of severe postpartum haemorrhage: initial report of a multicentre case series in Japan. Int J Hematol. 2012 Jan;95(1):57-63. doi: 10.1007/s12185-011-0974-9. Epub 2011 Dec 9.
- Background: PubMed 22630348Lin Y, Moltzan CJ, Anderson DR; National Advisory Committee on Blood and Blood Products. The evidence for the use of recombinant factor VIIa in massive bleeding: revision of the transfusion policy framework. Transfus Med. 2012 Dec;22(6):383-94. doi: 10.1111/j.1365-3148.2012.01164.x. Epub 2012 May 27.
- Background: PubMed 21239786Logan AC, Goodnough LT. Recombinant factor VIIa: an assessment of evidence regarding its efficacy and safety in the off-label setting. Hematology Am Soc Hematol Educ Program. 2010;2010:153-9. doi: 10.1182/asheducation-2010.1.153.
- Background: PubMed 22489992Palmason R, Vidarsson B, Sigvaldason K, Ingimarsson JP, Gudbjartsson T, Sigurdsson GH, Onundarson PT. Recombinant factor VIIa as last-resort treatment of desperate haemorrhage. Acta Anaesthesiol Scand. 2012 May;56(5):636-44. doi: 10.1111/j.1399-6576.2012.02688.x.
- Background: PubMed 23601765Spahn DR, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Filipescu D, Hunt BJ, Komadina R, Nardi G, Neugebauer E, Ozier Y, Riddez L, Schultz A, Vincent JL, Rossaint R. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care. 2013 Apr 19;17(2):R76. doi: 10.1186/cc12685.
- Background: PubMed 11103199Stainsby D, MacLennan S, Hamilton PJ. Management of massive blood loss: a template guideline. Br J Anaesth. 2000 Sep;85(3):487-91. doi: 10.1093/bja/85.3.487.
- Background: PubMed 21502651Yank V, Tuohy CV, Logan AC, Bravata DM, Staudenmayer K, Eisenhut R, Sundaram V, McMahon D, Olkin I, McDonald KM, Owens DK, Stafford RS. Systematic review: benefits and harms of in-hospital use of recombinant factor VIIa for off-label indications. Ann Intern Med. 2011 Apr 19;154(8):529-40. doi: 10.7326/0003-4819-154-8-201104190-00004.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chong Soon Eu, MD, MMed study chair
Universiti Sains Malaysia
Nurfatin Mohd Shah, BSc principal investigator
Universiti Sains Malaysia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Massive Hemorrhage and Massive Blood Loss, run by Universiti Sains Malaysia at 1 site in Malaysia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malaysia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in blood transfusion requirement (time frame: 24 hour before and after administration of rFVIIa). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03251547, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2018; AzTrials last refreshed its copy on 4 Nov 2026.