Coagulation Disorder, Coagulation Factor Deficiency, Hemorrhage, Postpartum Complication, Postpartum Hemorrhage
Conditions
Keywords
Postpartum hemorrhage, coagulation factor XIII
Brief summary
The goal of this trial is to determine if postpartum blood loss can be reduced by replenishing coagulation factor XIII (FXIII) at an early stage of postpartum hemorrhage (PPH). Summary of current body of evidence: * Morbidity and mortality due to PPH is rising. * Current guidelines focus on replenishment of fibrinogen as an initial step in the treatment of PPH-related coagulopathy, despite non-conclusive evidence in all prospective trials. * Trials from other specialties demonstrate a significant impact of FXIII on perioperative bleeding complications; a previous study at the University Hospital Zurich showed that pre-partum factor XIII activity had a strong association to postpartum blood loss. Therefore, this nationwide, multi-center, randomized, controlled trial in multiple perinatal centers across Switzerland will be conducted. The goal is to determine if postpartum blood loss and PPH-related complications can be reduced by replenishing FXIII. All participating women receive, according to the national guideline, 1g tranexamic acid (TXA) i.v. in case of PPH (measured blood loss \[MBL\] ≥ 500 mL) during the pre-study phase. Randomization takes place if bleeding continues and exceeds 700mL. The intervention group then receives FXIII (Fibrogammin®) according to approved dosage in addition to obstetric standard of care treatment for causes of PPH; the control group receives only standard of care treatment.
Detailed description
Postpartum hemorrhage (PPH) is a main reason for maternal mortality and morbidity. PPH, defined by the WHO as blood loss of 500 mL or more within 24 hours after delivery, causes about 30% of maternal deaths worldwide. The internationally observed trend towards increased PPH-related morbidity and mortality is disturbing and demands new strategies in the prevention and treatment of PPH. Although the most frequent causes for severe PPH are believed to be uterine atony or retained placenta, virtually all cases of severe PPH lead to a disorder of the coagulation system which itself aggravates bleeding. At the moment, most guidelines on coagulation management during PPH and expert opinions focus on the replenishment of coagulation factor I (fibrinogen) although three out of three randomized controlled trials with early or pre-emptive administration of fibrinogen during PPH were negative. Based on earlier research, it was hypothesized that coagulation factor XIII (FXIII) might play a significant role in women with increased postpartum blood loss, because of its role in the establishment of blood clot stability and fibrinolytic resistance. This hypothesis was tested in a prospective diagnostic study involving 1300 parturient women at the University Hospital Zurich and showed that pre-partum factor XIII activity had a strong association to postpartum blood loss. Therefore, this nationwide, multi-center, open-label, randomized controlled trial in major perinatal centers across Switzerland will be conducted. The goal is to determine if postpartum blood loss and PPH-related complications can be reduced by substitution of FXIII at an early stage of PPH. Irrespective of the answer to the question whether FXIII is effective in the treatment of PPH, this trial will contribute to enhancing the comprehension of coagulopathy in the context of PPH
Interventions
DRUGFibrogammin
Fibrogammin is administered according to the Summary of product characteristics (SmPC) after measured blood loss exceeds 700 ml and bleeding is ongoing
Sponsors
Christian Haslinger
Swiss National Science Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The analysis of the primary outcome will be performed using blinded treatment arms.
Intervention model description
multi- center, randomized, controlled
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* planned vaginal delivery * singleton vital pregnancy * gestational age at delivery \>= 30+0 weeks * maternal weight at admission for delivery \<100 kg
Exclusion criteria
* Antithrombotic therapy in pregnancy (therapeutic dosage) until admission for delivery (LMWH, UFH) * diagnosis of preeclampsia (ISSHP classification , eclampsia or HELLP syndrome), * known history of deep vein thrombosis or pulmonary embolism, * known diagnosis of bleeding disorder or thrombophilia, * known thrombocytopenia during second half of pregnancy with thrombocytes \< 100 G/L, * known anemia during second half of pregnancy with Hb\<80 g/L, * known sickle cell disease, * known malignant tumor(s), * participation in another study with investigational drug within the 30 days preceding and during the present study, * inability to follow the procedures of the study, e.g. due to language problems, * known or suspected non-compliance, drug or alcohol abuse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Loss during post partum hemorrhage | Day 1 (within 24 hours after delivery) | Measured blood loss, in ml |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Outcome of postpartum hemorrhage | Time point of assessment will be 48 hours (range 36 to 60) postpartum, if not stated otherwise | Composite of adverse maternal outcomes related to postpartum hemorrhage, including postpartum hemorrhage with measure blood loss ≥2000 mL (within 24 hours), admission to intensive care unit, blood transfusion, need for embolization of the pelvic arteries, laparotomy with surgical measures (such as compression sutures, or ligatures), or hysterectomy during hospitalization. |
| Changes in hematological standard value: hemoglobin | shortly before delivery and 48 hours (range 36 to 60 hours) after delivery | Comparison of hemoglobin values, pre-partum and post-partum (in g/L) |
| Changes in hematological standard value: leucocyte count | shortly before delivery and 48 hours (range 36 to 60 hours) after delivery | Comparison of leucocyte count, pre-partum and post-partum (in G/l) |
| Changes in hematological standard value; thrombocyte count | shortly before delivery and 48 hours (range 36 to 60 hours) after delivery | Comparison of thrombocyte count, pre-partum and post-partum (in G/l) |
| Hospital costs | from admission to hospital until hospital discharge, up to 9 weeks | Total costs (in CHF) |
| Breastfeeding | 6 - 9 weeks after delivery | Number of women who exclusively breastfeed their babies after PPH |
| Patient survey (in a subgroup of patients only) | discharge from hospital, estimated 3 - 5 days after delivery | Questionnaire for personal experience during PPH |
Countries
Switzerland
Contacts
CONTACTChristian Haslinger, Prof. Dr
CONTACTAnnick Toggenburger, PhD
STUDY_CHAIRChristian Haslinger, Prof. Dr.
University of Zurich
PRINCIPAL_INVESTIGATORSara de Oliveira, MD
University Hospital, Geneva
PRINCIPAL_INVESTIGATORHélène Legardeur, MD
University of Lausanne Hospitals
PRINCIPAL_INVESTIGATORBeatrice Mosimann, Prof. Dr.
University Hospital, Basel, Switzerland
PRINCIPAL_INVESTIGATORTina Fischer, MD
HOCH Health Ostschweiz
PRINCIPAL_INVESTIGATORLeonhard Schäffer, Prof. Dr.
Kantonsspital Baden
PRINCIPAL_INVESTIGATORMichael Winter, MD
Spital Zollikerberg
PRINCIPAL_INVESTIGATORJarmila Zdanowicz, MD
Inselspital-University Hospital Bern
PRINCIPAL_INVESTIGATORLeila Sultan-Beyer, MD
Cantonal Hospital Winterthur
Outcome results
None listed