Condition category
Pregnancy and Childbirth
Date applied
04/06/2013
Date assigned
01/07/2013
Last edited
27/04/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Bleeding at the time of childbirth (postpartum haemorrhage, PPH) is a major cause of death. Bleeding is caused when the uterus fails to contract or by operations. This is made worse by damage of blood clotting system. A number of studies have shown that low levels of a blood clotting factor called fibrinogen is associated with worse bleeding, the need for surgical measures and the need for blood transfusion (taking blood from one person and giving to other). This study will find out whether giving fibrinogen early during bleeding at the time of childbirth reduces blood loss.

Who can participate?
Women experiencing major postpartum haemorrhage (PPH) can participate in this study.

What does the study involve?
Participating women are randomly allocated to one of two groups. One group will receive fibrinogen concentrate injected into the vein and the other group will receive a placebo (dummy). All participants will be contacted via telephone after 6 weeks by a midwife.

What are the possible benefits and risks of participating?
We hope that giving fibrinogen will reduce blood loss, so there may be a benefit to the participant from taking part in this study. We hope that the results may help to improve the treatment of women who experience similar blood loss at the time of childbirth in the future. Fibrinogen is not a new treatment and it has been used in patients who have low levels of fibrinogen for many years, but its use in bleeding at the time of childbirth is relatively new. There is no evidence to suggest that fibrinogen has any serious side effects when used during childbirth but, because it is not routinely used at this time, we may not know all the possible side effects. The idea of giving women fibrinogen is to thicken the blood to stop bleeding but it is possible that this may cause clots where they are not needed and we will be especially looking for this.

Where is the study run from?
The study will be run from four centres in the UK: Cardiff and Vale University Health Board, Leicester Royal Infirmary, University College Hospital London and Liverpool Women's Hospital NHS Foundation Trust.

When is the study starting and how long is it expected to run for?
Recruitment starts in June 2013 and will end in September 2014. Participating women will be followed up for 6 weeks.

Who is funding the study?
CSL Behring, UK.

Who is the main contact?
Dr Peter Collins
Peter.collins@wales.nhs.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Peter Collins

ORCID ID

Contact details

Dept of Haematology
School of Medicine
Cardiff University
Heath Park
Cardiff
CF14 4XN
United Kingdom
-
peter.collins@wales.nhs.uk

Additional identifiers

EudraCT number

2012-005511-11

ClinicalTrials.gov number

Protocol/serial number

SPON 1155-12

Study information

Scientific title

Fibrinogen concentrate versus placebo for treatment of postpartum haemorrhage: a multicentre, prospective, double blind randomised controlled trial

Acronym

OBS2

Study hypothesis

Infusion of fibrinogen concentrate early during a moderately severe and ongoing postpartum haemorrhage, in women with a reduced fibrinogen, as measured by the FIBTEM A5 test, will reduce the total number of allogeneic blood products (red blood cells, fresh frozen plasma, platelet concentrates and cryoprecipitate) transfused after study medication until discharge.

Ethics approval

Scotland A Research Ethics Committee, 26/03/2013, ref: 13/SS/0008

Study design

Prospective randomised double-blind placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Reproductive Health & Childbirth

Intervention

Participants randomised to receive either a bolus infusion of fibrinogen concentrate or placebo. Fibrinogen concentrate will be supplied as a lyophilised powder in glass bottles each containing 1 gm of fibrinogen. The fibrinogen will be dissolved in 50 mL of sterile water before infusion. The matching placebo will be an equal volume of normal saline.
Dose: Between 2 g and 8 g (administered intravenously) depending on the ideal weight for height of the woman and measured Fibtem level. Women who are randomised to receive fibrinogen concentrate or placebo will be contacted by telephone after 6 weeks by a research midwife or other study team member.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

The total number of allogeneic blood products (red blood cells + fresh frozen plasma (FFP) + cryoprecipitate + platelets) transfused after study medication until discharge, compared to placebo.

Secondary outcome measures

To explore the effect of fibrinogen concentrate infusion on the following efficacy endpoints:
1. The proportion of women receiving no allogeneic blood products until discharge and within 24 hours after study medication
2. The number of units of red blood cells, FFP, platelets and cryoprecipitate transfused within
24 hours after study medication and until discharge
3. The measured abnormal blood loss within 24 hours after study medication and until discharge
4. The change in Clauss fibrinogen and FIBTEM parameters before and 15 minutes and 24
hours after the study medication
5. The proportion of women requiring cryoprecipitate or fibrinogen concentrate as subsequent
therapy within 24 hours after study medication and until discharge
6. The proportion of women requiring invasive procedures (return to theatre, uterine brace
sutures, uterine tamponade balloons, radiology intervention and hysterectomy) and the time
of this intervention within 24 hours after study medication and until discharge
7. Incidence , duration and reasons for not exclusive breastfeeding

To explore the effect of fibrinogen concentrate infusion on following safety endpoints:
1. The proportion of women requiring ITU/HDU admission and length of stay
2. The total length of hospital stay
3. The incidence of clinically diagnosed arterial and venous thromboembolism within 6 weeks
of study medication

Overall trial start date

01/06/2013

Overall trial end date

30/09/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age 18 years or over
2. Women should have any one of the following within the first 12 hours after delivery:
2.1. Haemorrhage of about 1500 ml and ongoing bleeding without another complication
2.2. Haemorrhage of about 1000 mL and ongoing bleeding with any of:
2.2.1. caesarean section
2.2.2. uterine atony
2.2.3. placental abruption*
2.2.4. placenta praevia
2.2.5. Cardiovascular instability (arterial blood pressure below 90 mm/Hg and heart rate greater than 100 bpm)
2.2.6. Clinical observation of microvascular oozing
* If in the event of a placental abruption, women may be recruited if there is less than
1000ml visible blood loss, because bleeding at the time of abruption maybe concealed.
3. Women can be included if they fulfil the inclusion criteria after delivery of the baby but
where the bleeding had started in the antenatal period (antepartum haemorrhage)
4. Women can be included where there is a slow accumulation of on-going blood loss (in the
first 12 hours after delivery) if they fulfil the inclusion criteria

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

About 1050 women will be recruited into the observational phase of the study so that 60 can be randomised to receive fibrinogen concentrate or placebo.

Participant exclusion criteria

1. Women who have documented that they do not want to participate in the study during
the antenatal period
2. Women declining infusion of red blood cells or blood components
3. Known inherited bleeding disorder
4. Placenta accreta diagnosed antenatally
5. Women who have already received uterine brace sutures, uterine tamponade balloons,
radiology intervention or hysterectomy before entering the study
6. Clinical suspicion of amniotic fluid embolism
7. Secondary postpartum haemorrhage (haemorrhage which starts >12 hours after delivery)

Recruitment start date

01/06/2013

Recruitment end date

30/09/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cardiff University
Cardiff
CF14 4XN
United Kingdom

Sponsor information

Organisation

Cardiff University (UK)

Sponsor details

30-36 Newport Road
Cardiff
CF24 0DE
United Kingdom
-
shawc3@cf.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Industry

Funder name

CSL Behring (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2015 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/25906770

Publication citations

Additional files

Editorial Notes