Allow infusion of fibrinogen at any rate at the discretion of the clinician. Clearly state that FFP can be given as soon as it arrives. State that the IDMC will meet after fewer patients have been randomised. The IDMC will also be asked to focus on thrombotic episodes and infusion reactions.

The use of A5 instead of MCF to enter the interventional phase. The primary and secondary outcomes. Originally the primary outcome was 'Total number of allogeneic blood products transfused within 24 hours after study medication'. This has now been changed to 'Total number of allogeneic blood products transfused after study medication until discharge' A FIBTEM test at 24 hours has been added. Data is collected electronically as oppose to paper based. In the event death: the unblinding procedure has now been changed; approval has to be sought from SEWTU prior to carrying out unblinding Intention to Treat (ITT) added to statistical section. Additional FIBTEM and coagulation screen will be taken at 24 hours after the study medication. Minor wording change in section 8.2 exclusion criteria, “stated” is changed to “documented”. Wording change section 11 withdrawal and loss to follow-up. “The patient may withdraw or be withdrawn from the observational phase and do not proceed to the interventional phase” The following sentence has been removed “If placenta accreta is diagnosed during the surgery, the patient will not be included in the efficacy analysis. Section 14.2: Previous PPH has been added to the list of data to be collected in the study and to the CRF

Substantial amendment/clarification to the inclusion criteria: Women can be included in the observational phase before delivery but cannot be randomised in the interventional phase until after delivery. For ease of use Fibrinogen concentrate to treat postpartum haemorrhage is referred to as OBS2 (Obstetrics Bleeding Study 2) Addition of co-investigators and change in some of trial team’s details.

Secondary outcomes clarified: 1) The total number of units of red blood cells, FFP, platelets and cryoprecipitate transfused within 24 hours after study medication. The volume of cell salvaged blood transfused within 24 hours and until discharge (250 mL cell salvaged blood will be considered equivalent to 1 unit of red blood cells.) The total number of units of red blood cells, FFP, platelets and cryoprecipitate plus 1 unit for every 250 mL cell salvage transfused within 24 hours after study medication and until discharge Change definitions of invasive procedures. 2)Withhold FFP if bleeding stopping 3) Inclusion criteria. Gestation ≥24+0 weeks 4) Informed consent. If the woman has received the antenatal leaflet but didn’t indicate whether should would wish to participate in the study or not, she may be approached to enter the study. 5) Tranexamic acid may be infused at any time during the observational phase according to the treating clinicians’ discretion. 6) Allocation of study medication. If, in the opinion of the treating clinician, it would not be safe to administer placebo at the time of randomisation, the woman will not enter the interventional phase but will be treated at the discretion of the clinician. This may include the use of fibrinogen concentrate from routine stocks. All data will continue to be collected and the reason for not randomising will be recorded. 7) Unblinding in the event of death or adverse event. Unblinding can be done through the OBS2 online database. 8) Study treatments. The study centres can request an appropriate number of study medication pack when the study medication level reaches 3 study medication packs. 9) Pre-medication. Tranexamic acid should be given before or as soon as practical after study treatment. 10) SAEs reporting to CSL (within 24 hours of the sponsor being made aware of them). 11) Flow chart for adverse event reporting procedure has been amended.

Pharmacovigilance: -Day zero is defined as the day an SAE form is received at SEWTU. -The assignment of the causality should be made by the Investigator responsible for the care of the participant. The Chief Investigator (Clinical Reviewer Delegate) will also be responsible for making an assessment of causality. -The assessment of whether or not an adverse reaction is an expected reaction from the administration of the IMP will be provided by the Chief Investigator (or Clinical Reviewer Delegate), it will not be provided by the Investigator responsible for the care of the participant. - The responsible investigator should sign the causality of the event. No assessment of expectedness will be provided by the Investigator responsible for the care of the participant.

Further information has been provided by the manufacturer (CSL Behring) in relation to temperature storage of IMP. Hence section 12.1 has been amended: Fibrinogen concentrate and placebo in study packs will be stored according to manufacturer’s instructions (Investigator’s Brochure 2011 & communication with CSL Behring, December 2013).

Further information has been provided by the manufacturer (CSL Behring) in relation to temperature storage of IMP. Hence section 12.1 has been amended: Fibrinogen concentrate and placebo in study packs will be stored according to manufacturer’s instructions (Investigator’s Brochure 2011 & communication with CSL Behring, December 2013).

-Number of participants in the observational arm amended to approximately 450 women. -Minor amendments to section 15.2 (sample size). -Withdrawal: form completed on the online database -6 week follow-up: telephone or face to face

-SAE: form completed on the online database -Contingency plan in the event of a system failure (online database) -Procedure to obtain outcome data in the event of non-contact at 6 weeks (interventional phase)

-Planned trial period changed to December 2014 (was September 2014) - Section 12.1: Minimum and maximum temperature will be monitored weekly (was daily

-Planned trial period changed to October 2015 (was December 2014). - Minimum stock level at sites changed to 2 IMP packs - Adding an expression of interest form to ask participants whether they would be interested in taking part in other studies related to post-partum haemorrhage, including their experience in the Obstetrics Bleeding Study (OBS2).

-Planned trial period changed to October 2016 (was December 2014). - Inclusion of a qualitative sub-study to explore participants, legal representatives and health professionals’ experiences and attitudes towards the consent process in the Obstetric Bleeding Study (OBS2).