Trial Outcomes & Findings for Fibrinogen in Haemorrhage of Delivery (NCT NCT02155725)

Last Updated: 2020-09-25

Results Overview

The primary efficacy variable is a binary (Failure versus Success) composite endpoint. Failure is defined when a patient: * loses at least 4 g/dL of Hb compared to the reference Hb level , AND/OR * requires the transfusion of at least 2 units of packed RBCs.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

448 participants

Primary outcome timeframe

Evaluation of the two criteria that form the primary endpoint within the 48 h following the administration

Results posted on

2020-09-25

Participant Flow

Between 10 April 2014 and 20 June 2018, 448 patients from 30 sites signed an informed consent.

During the pre-assigment period 11 patients withdrawn before treatment period. (1 treated with another IMP, 5 not treated, 2 no emergency consent signed, 1 no post inclusion consent signed, 2 refused to continue the study)

Participant milestones

Participant milestones
Measure	Clottafact Human fibrinogen concentrate 3g intravenous use. 2 vials of 1,5 g/100mL, each vial of powder was reconstituted with 100 mL of sterile water for injection.	Placebo Placebo intravenous use. 2 vials of 100 mL, each vial of powder was reconstituted with 100 mL of sterile water.
Treatment Period STARTED	224	213
Treatment Period COMPLETED	224	213
Treatment Period NOT COMPLETED	0	0
Follow-up Period STARTED	224	213
Follow-up Period COMPLETED	207	202
Follow-up Period NOT COMPLETED	17	11

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clottafact n=224 Participants Human fibrinogen concentrate 3g intravenous use. 2 vials of 1,5 g/100mL, each vial of powder was reconstitued with 100 mL of sterile water for injection.	Placebo n=213 Participants Placebo intravenous use. 2 vials of 100 mL, eache vial of powder was reconttitued with 100 mL of sterile water for injection.	Total n=437 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=224 Participants	0 Participants n=213 Participants	0 Participants n=437 Participants
Age, Categorical Between 18 and 65 years	224 Participants n=224 Participants	213 Participants n=213 Participants	437 Participants n=437 Participants
Age, Categorical >=65 years	0 Participants n=224 Participants	0 Participants n=213 Participants	0 Participants n=437 Participants
Age, Continuous	30.5 years STANDARD_DEVIATION 5.6 • n=224 Participants	30.3 years STANDARD_DEVIATION 5.4 • n=213 Participants	30.4 years STANDARD_DEVIATION 5.5 • n=437 Participants
Sex: Female, Male Female	224 Participants n=224 Participants	213 Participants n=213 Participants	437 Participants n=437 Participants
Sex: Female, Male Male	0 Participants n=224 Participants	0 Participants n=213 Participants	0 Participants n=437 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: Evaluation of the two criteria that form the primary endpoint within the 48 h following the administration

Population: Number of patients with failure

Outcome measures

Outcome measures
Measure	Per Protocole (PP) Set Clottafact n=195 Participants Patients with no missing data for the primary criterion.	Per Protocole (PP) Set Placebo n=193 Participants Patients with no missing data for the primary criterion.	Intention To Treat (ITT) Set Clottafact n=224 Participants All patients treated with Clottafact. (patients who received at least one infusion of Clottafact)	Intention To Treat (ITT) Set Placebo n=213 Participants All patients treated with Placebo. (patients who received at least one infusion of placebo)	Full Analysis Set (FAS) Clottafact n=220 Participants Patients treated with Clottafact of the ITT Set with no missing data for the primary criteria.	Full Analysis Set (FAS) Placebo n=210 Participants Patients treated with Placebo of the ITT Set with no missing data for the primary criteria.
Failure Rate of PPH Management	75 Participants	80 Participants	92 Participants	92 Participants	88 Participants	89 Participants

SECONDARY outcome

Timeframe: from H0 to Day 2

Considering failure as the fact of requiring at least 2 units of RBCs.

Outcome measures

Outcome measures
Measure	Per Protocole (PP) Set Clottafact n=220 Participants Patients with no missing data for the primary criterion.	Per Protocole (PP) Set Placebo n=210 Participants Patients with no missing data for the primary criterion.	Intention To Treat (ITT) Set Clottafact All patients treated with Clottafact. (patients who received at least one infusion of Clottafact)	Intention To Treat (ITT) Set Placebo All patients treated with Placebo. (patients who received at least one infusion of placebo)	Full Analysis Set (FAS) Clottafact Patients treated with Clottafact of the ITT Set with no missing data for the primary criteria.	Full Analysis Set (FAS) Placebo Patients treated with Placebo of the ITT Set with no missing data for the primary criteria.
Patients With at Least Administration of 2 Units of RBCs	51 Participants	52 Participants	—	—	—	—

SECONDARY outcome

Timeframe: From reference value to Day 2

Considering failure as the fact of having lost at least 4 g/dL of Hb.

Outcome measures

Outcome measures
Measure	Per Protocole (PP) Set Clottafact n=220 Participants Patients with no missing data for the primary criterion.	Per Protocole (PP) Set Placebo n=210 Participants Patients with no missing data for the primary criterion.	Intention To Treat (ITT) Set Clottafact All patients treated with Clottafact. (patients who received at least one infusion of Clottafact)	Intention To Treat (ITT) Set Placebo All patients treated with Placebo. (patients who received at least one infusion of placebo)	Full Analysis Set (FAS) Clottafact Patients treated with Clottafact of the ITT Set with no missing data for the primary criteria.	Full Analysis Set (FAS) Placebo Patients treated with Placebo of the ITT Set with no missing data for the primary criteria.
Patients With Loss of at Least 4 g/dL of Hb	42 Participants	41 Participants	—	—	—	—

Adverse Events

Clottafact

Serious events: 10 serious events

Other events: 95 other events

Deaths: 0 deaths

Placebo

Serious events: 10 serious events

Other events: 106 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director France

LFB Biomédicaments

Phone: 33 169827229

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Clottafact n=224 participants at risk Human fibrinogen concentrate 3g intravenous use. 2 vials of 1,5 g/100mL, each vial of powder was reconstitued with 100 mL of sterile water for injection.	Placebo n=213 participants at risk Placebo intravenous use. 2 vials of 100 mL, eache vial of powder was reconttitued with 100 mL of sterile water.
Vascular disorders Aneurysm	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Vascular disorders Blood pressure inadequately controlled	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Vascular disorders Hypotension	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Vascular disorders Shock haemorrhagic	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Vascular disorders Thrombosis	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Vascular disorders Venous thrombosis limb	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Investigations Blood alkaline phosphatase increased	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Investigations Blood pressure ambulatory increased	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Investigations Blood uric acid increased	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Nervous system disorders Headache	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Pregnancy, puerperium and perinatal conditions HELLP syndrome	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Pregnancy, puerperium and perinatal conditions Postpartum haemorrhage	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Pregnancy, puerperium and perinatal conditions Retained placenta or membranes	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Eye disorders Vision blurred	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
General disorders Discomfort	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
General disorders Oedema peripheral	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
General disorders Pyrexia	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Psychiatric disorders Psychological trauma	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Reproductive system and breast disorders Broad ligament haematoma	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Reproductive system and breast disorders Metrorrhagia	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Reproductive system and breast disorders Uterine haematoma	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Reproductive system and breast disorders Uterine necrosis	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Reproductive system and breast disorders Uterine rupture	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Hepatobiliary disorders Acute fatty liver of pregnancy	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Metabolism and nutrition disorders Hyperglycaemia	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Infections and infestations Amniotic cavity infection	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Infections and infestations Endometritis decidual	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Infections and infestations Pyelonephritis acute	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).

Measure	Clottafact n=224 participants at risk Human fibrinogen concentrate 3g intravenous use. 2 vials of 1,5 g/100mL, each vial of powder was reconstitued with 100 mL of sterile water for injection.	Placebo n=213 participants at risk Placebo intravenous use. 2 vials of 100 mL, eache vial of powder was reconttitued with 100 mL of sterile water.
Vascular disorders Hypertension	1.3% 3/224 • Number of events 3 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	2.8% 6/213 • Number of events 6 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Vascular disorders Hypotension	2.2% 5/224 • Number of events 5 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	1.9% 4/213 • Number of events 4 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Nervous system disorders Dizziness	0.89% 2/224 • Number of events 2 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	1.4% 3/213 • Number of events 3 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Nervous system disorders Headache	2.2% 5/224 • Number of events 6 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	3.3% 7/213 • Number of events 8 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
General disorders Hyperthermia	0.89% 2/224 • Number of events 2 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	2.3% 5/213 • Number of events 5 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
General disorders Influenza like illness	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	1.4% 3/213 • Number of events 3 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
General disorders Oedema peripheral	1.8% 4/224 • Number of events 4 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	2.8% 6/213 • Number of events 6 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
General disorders Pyrexia	4.9% 11/224 • Number of events 11 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	5.6% 12/213 • Number of events 12 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
General disorders Malaise	0.89% 2/224 • Number of events 2 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	1.9% 4/213 • Number of events 4 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Psychiatric disorders Anxiety	1.3% 3/224 • Number of events 3 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Gastrointestinal disorders Abdominal pain	1.8% 4/224 • Number of events 4 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.47% 1/213 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Gastrointestinal disorders Constipation	4.0% 9/224 • Number of events 9 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	1.9% 4/213 • Number of events 4 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Gastrointestinal disorders Haemorrhoids	9.4% 21/224 • Number of events 21 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	13.6% 29/213 • Number of events 29 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Gastrointestinal disorders Nausea	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	1.9% 4/213 • Number of events 4 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Gastrointestinal disorders Vomiting	0.45% 1/224 • Number of events 1 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	1.9% 4/213 • Number of events 4 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Reproductive system and breast disorders Metrorrhagia	2.7% 6/224 • Number of events 6 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	1.4% 3/213 • Number of events 3 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Reproductive system and breast disorders Nipple disorder	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	1.9% 4/213 • Number of events 4 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Reproductive system and breast disorders Oedema genital	0.89% 2/224 • Number of events 2 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	2.3% 5/213 • Number of events 5 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Reproductive system and breast disorders Uterine pain	1.8% 4/224 • Number of events 4 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Reproductive system and breast disorders Vulval oedema	0.00% 0/224 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	1.9% 4/213 • Number of events 4 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Hepatobiliary disorders Hepatocellular injury	1.3% 3/224 • Number of events 3 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Musculoskeletal and connective tissue disorders Back pain	1.3% 3/224 • Number of events 3 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	1.9% 4/213 • Number of events 4 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Infections and infestations Endometritis decidual	1.8% 4/224 • Number of events 4 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	2.3% 5/213 • Number of events 5 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Infections and infestations Puerperal pyrexia	3.1% 7/224 • Number of events 7 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	1.9% 4/213 • Number of events 4 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).
Infections and infestations Urinary tract infection	1.8% 4/224 • Number of events 4 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).	0.00% 0/213 • The safety was assessed by recording all AEs occurring during the study, from signature of the informed consent to last study visit (6 +/- 2 weeks after delivery).