PCC and Fibrinogen Compared With FFP in PPH

Study Overview
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Brief Summary
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The purpose of the study is to find out if the regimen of prothrombin complex concentrate (PCC) together with fibrinogen concentrate is as efficient as fresh frozen plasma (FFP) (plus fibrinogen if needed) during the early stages of the transfusion therapy in postpartum haemorrhage (PPH). The original protocol included the use of HES and the recruitment of patients was postponed while waiting the final decision by EMA. All HES solutions were abandoned at our institution in September and an amendment was made to change the protocol. HES solution are replaced by the use of hyperoncotic (20%) albumin.

Detailed Description
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Forty patients are randomized to receive either PCC and fibrinogen concentrate (PCC group) or FFP (and fibrinogen if needed) (FFP group), 20 patients in each group. Patients in the PCC group receive 15 IU/kg of PCC concentrate and 2 g of fibrinogen concentrate. Patients in the FFP group receive 4 units of FFP. In both groups, additional fibrinogen is administered (if needed) to increase the baseline FIBTEM-MCF (at 5 min) to the target of 15 mm. Baseline blood samples will be drawn at study inclusion when the (on-going) blood loss exceeds 1500 ml. The next samples will be drawn at 45 min (or immediately after the administration of the study drug if later). Otherwise, the management protocol strictly follows the local PPH guideline. The primary endpoint is the amount of blood loss within the first 6 and 24 hours after delivery. Secondary endpoints include the difference/similarity in the laboratory determinations (ia coagulation screen, PFA-100, CAT and ROTEM).

Official Title
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Use of Prothrombin Complex Concentrate and Fibrinogen Compared With Fresh Frozen Plasma (and Fibrinogen if Needed) in the Treatment of Postpartum Haemorrhage

Conditions
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Postpartum Haemorrhage

Intervention / Treatment
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* Drug: PCC
* Drug: FFP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women who have delivered vaginally or by caesarean section with a PPH of 2000 ml (the amount of blood loss: in addition to the suctioned blood, sponges, wraps, swabs, etc. are carefully weighed) Exclusion Criteria: Women with a history of bleeding tendency or hepatic or renal insufficiency, or PPH exceeding 3000 ml because in that case the initial need for fibrinogen may be even more

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PCC group<br>Twenty patients in the PCC group receive 15 IU/kg of Octaplex concentrate and 2 g of Riastap concentrate. Additional fibrinogen is administered (if needed) to increase the baseline FIBTEM-MCF (at 5 min) to the target of 15 mm. | Drug: PCC<br>* 15 IU/kg Octaplex and 2 g Riastab. Additional fibrinogen if needed.<br>* Other names: Octaplex, Riastab;|
| Active Comparator: FFP group<br>Twenty patients in the FFP group receive 4 units of FFP (Octaplas). Additional fibrinogen (Riastab) is administered (if needed) to increase the baseline FIBTEM-MCF (at 5 min) to the target of 15 mm. The fibrinogen content of the FFP will be taken into consideration (2.1 g in 4 units of FFP). | Drug: FFP<br>* 4 units Octaplas. Additional fibrinogen if needed.<br>* Other names: Octaplas;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood loss | The suctioned blood is recorded and sponges, wraps, swabs, etc. are carefully weighed. The amount of blood loss will be compared between the groups. | Within the first 6 and 24 hours after delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum clot firmness (MCF) | INTEM, EXTEM, FIBTEM and APTEM / ROTEM | At the time when the blood loss exceeds 1500 ml and 45 min later | 
| Endogenous thrombin potential | CAT | At the time when the blood loss exceeds 1500 ml and 45 min later | 
| Fibrinogen level | Clauss method | At the time when the blood loss exceeds 1500 ml and 45 min later | 
| Platelet function | PFA-100 | At the time when the blood loss exceeds 1500 ml and 45 min later | 
| Clotting time (CT) | INTEM, EXTEM, FIBTEM and APTEM / ROTEM | At the time when the blood loss exceeds 1500 ml and 45 min later | 
| Clot formation time (CFT) | INTEM, EXTEM, FIBTEM and APTEM / ROTEM | At the time when the blood loss exceeds 1500 ml and 45 min later |