SWIFT - SWIss Factor XIII Trial in PPH (SWIFT)

Early Factor XIII Replacement in Postpartum Hemorrhage: Multi-center, Randomized, Controlled, Investigator-initiated Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Hemorrhage; Coagulation Disorder; Postpartum Hemorrhage; Postpartum Complication; Coagulation Factor Deficiency
• Intervention / Treatment: Drug: Fibrogammin

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

• Study Type: Interventional
• Enrollment (Estimated): 988
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Annick Toggenburger, PhD; Email: annick.toggenburger-schroeder@usz.ch
• Study Contact Backup: Name: Christian Haslinger, Prof. Dr; Phone Number: 0041 432537575; Email: Christian.haslinger@usz.ch

Study Locations

• Switzerland
  • Baden, Switzerland, 5404
    • Recruiting
    • Cantonal Hospital Baden
    • Contact: Leonhard Schäffer, Prof. Dr.; Email: Leonhard.Schaeffer@ksb.ch
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel
    • Contact: Beatrice Mosimann, Prof. Dr.; Email: beatrice.mosimann@usb.ch
  • Bern, Switzerland, 3010
    • Recruiting
    • Inselspital-University Hospital Bern
    • Contact: Jarmila Zdanowicz; Email: jarmila.zdanowicz@insel.ch
  • Lausanne, Switzerland, 1005
    • Recruiting
    • University Hospital Lausanne
    • Contact: David Baud, MD PhD; Email: david.baud@chuv.ch
    • Contact: Helene Legardeur; Email: helene.legardeur@chuv.ch
  • Sankt Gallen, Switzerland, 9007
    • Recruiting
    • Cantonal Hospital St. Gallen
    • Contact: Tina Fischer, MD; Email: tina.fischer@kssg.ch
  • Canton of Geneva
    • Geneva, Canton of Geneva, Switzerland, 1205
      • Not yet recruiting
      • University Hospital Geneva
      • Contact: Begoña Martinez de Tejada, MD PhD; Email: begona.martinezdetejada@hcuge.ch
  • Canton of Zurich
    • Winterthur, Canton of Zurich, Switzerland, 8401
      • Recruiting
      • Cantonal Hospital Winterthur
      • Contact: Leila Sultan-Beyer, MD; Email: leila.sultan-beyer@ksw.ch
    • Zollikerberg, Canton of Zurich, Switzerland, 8125
      • Recruiting
      • Spital Zollikerberg
      • Contact: Michael Winter, MD; Email: michael.winter@spitalzollikerberg.ch
    • Zurich, Canton of Zurich, Switzerland, 8091
      • Recruiting
      • University Hospital of Zürich
      • Contact: Annick Toggenburger, PhD; Email: annick.toggenburger-schroeder@usz.ch
      • Contact: Christian Haslinger, Prof. Dr.; Phone Number: 0041 432537575; Email: Christian.haslinger@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Exclusion criteria prior randomization

• Maternal fever ≥39.0°C
• unplanned cesarean delivery is performed,
• Measured Blood Loss remains < 700 mL after administration of 1g tranexamic acid .
• Postpartum hemorrhage due to occult bleeding (intra-abdominal, retroperitoneal, parametric),

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fibrogammin (FXIII); Women in the intervention group receive FXIII intravenously in addition to the standard of care treatment for PPH. FXIII is administered when blood loss is > 700 ml. Women weighing <80 kg receive 1250 IU Fibrogammin®; women weighing 80-99.9 kg receive 1500 IU Fibrogammin®; thus ensuring a dose of 15-20 IU FXIII per kg body weight according to the manufacturer's recommendation.	Drug: Fibrogammin; Fibrogammin is administered according to the Summary of product characteristics (SmPC) after measured blood loss exceeds 700 ml and bleeding is ongoing; Other Names: Factor XIII
No Intervention: Control; Women in the control group will be treat according to the standard of care procedure for PPH.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Loss during post partum hemorrhage	Measured blood loss, in ml	Day 1 (within 24 hours after delivery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital costs	Total costs (in CHF)	from admission to hospital until hospital discharge, up to 9 weeks
Patient survey (in a subgroup of patients only)	Questionnaire for personal experience during PPH	discharge from hospital, estimated 3 - 5 days after delivery
Outcome of postpartum hemorrhage	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.	Time point of assessment will be 48 hours (range 36 to 60) postpartum, if not stated otherwise
Changes in hematological standard value: hemoglobin	Comparison of hemoglobin values, pre-partum and post-partum (in g/L)	shortly before delivery and 48 hours (range 36 to 60 hours) after delivery
Changes in hematological standard value: leucocyte count	Comparison of leucocyte count, pre-partum and post-partum (in G/l)	shortly before delivery and 48 hours (range 36 to 60 hours) after delivery
Changes in hematological standard value; thrombocyte count	Comparison of thrombocyte count, pre-partum and post-partum (in G/l)	shortly before delivery and 48 hours (range 36 to 60 hours) after delivery
Breastfeeding	Number of women who exclusively breastfeed their babies after PPH	6 - 9 weeks after delivery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thromboembolic events	Number of thromboembolic events (safety outcome)	6 - 9 weeks after delivery (visit 4)

Collaborators and Investigators

• Sponsor: Christian Haslinger
• Collaborators: Swiss National Science Foundation
• Investigators: Study Chair: Christian Haslinger, Prof. Dr., University of Zurich; Principal Investigator: Beatrice Mosimann, Prof. Dr., University Hospital, Basel, Switzerland; Principal Investigator: Leonhard Schäffer, Prof. Dr., Kantonsspital Baden; Principal Investigator: Michael Winter, MD, Spital Zollikerberg; Principal Investigator: Leila Sultan-Beyer, MD, Cantonal Hospital Winterthur; Principal Investigator: Jarmila Zdanowicz, MD, Inselspital-University Hospital Bern; Principal Investigator: Sara de Oliveira, MD, University Hospital, Geneva; Principal Investigator: Hélène Legardeur, MD, University of Lausanne Hospitals; Principal Investigator: Tina Fischer, MD, Hoch Health Ostschweiz

Publications and helpful links

General Publications

• Say L, Chou D, Gemmill A, Tuncalp O, Moller AB, Daniels J, Gulmezoglu AM, Temmerman M, Alkema L. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014 Jun;2(6):e323-33. doi: 10.1016/S2214-109X(14)70227-X. Epub 2014 May 5.
• WHO Recommendations for the Prevention and Treatment of Postpartum Haemorrhage. Geneva: World Health Organization; 2012. Available from http://www.ncbi.nlm.nih.gov/books/NBK131942/
• Weeks A. The prevention and treatment of postpartum haemorrhage: what do we know, and where do we go to next? BJOG. 2015 Jan;122(2):202-10. doi: 10.1111/1471-0528.13098. Epub 2014 Oct 7.
• GBD 2015 Maternal Mortality Collaborators. Global, regional, and national levels of maternal mortality, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016 Oct 8;388(10053):1775-1812. doi: 10.1016/S0140-6736(16)31470-2. Erratum In: Lancet. 2017 Jan 7;389(10064):e1. doi: 10.1016/S0140-6736(16)32609-5.
• Korte WC, Szadkowski C, Gahler A, Gabi K, Kownacki E, Eder M, Degiacomi P, Zoller N, Devay J, Lange J, Schnider T. Factor XIII substitution in surgical cancer patients at high risk for intraoperative bleeding. Anesthesiology. 2009 Feb;110(2):239-45. doi: 10.1097/ALN.0b013e318194b21e.
• Wettstein P, Haeberli A, Stutz M, Rohner M, Corbetta C, Gabi K, Schnider T, Korte W. Decreased factor XIII availability for thrombin and early loss of clot firmness in patients with unexplained intraoperative bleeding. Anesth Analg. 2004 Nov;99(5):1564-1569. doi: 10.1213/01.ANE.0000134800.46276.21.
• Haslinger C, Korte W, Hothorn T, Brun R, Greenberg C, Zimmermann R. The impact of prepartum factor XIII activity on postpartum blood loss. J Thromb Haemost. 2020 Jun;18(6):1310-1319. doi: 10.1111/jth.14795. Epub 2020 Apr 16.
• Haslinger C, Hothorn T, Bossung V, Kalimeris S, Ranieri E, Ochsenbein-Koelble N, Korte W. Effects of early factor XIII replacement in postpartum hae morrhage: study protocol for a multicentre, open-label, randomised, controlled, investigator-initiated trial. BMJ Open. 2025 May 8;15(5):e100262. doi: 10.1136/bmjopen-2025-100262.

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: May 31, 2024
• First Submitted That Met QC Criteria: June 28, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Postpartum hemorrhage; coagulation factor XIII
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor Complications; Pregnancy Complications; Hematologic Diseases; Hemorrhagic Disorders; Puerperal Disorders; Uterine Hemorrhage; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Postpartum Hemorrhage; Hemorrhage; Hemostatic Disorders; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Hydrolases; Enzymes; Enzymes and Coenzymes; Blood Proteins; Endopeptidases; Peptide Hydrolases; Serine Endopeptidases; Serine Proteases; Blood Coagulation Factors; Enzyme Precursors; Protein Precursors; Fibrinolysin; Factor XIII
• Other Study ID Numbers: BASEC 2024 - 00374

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing plan aims to ensure computational reproducibility of all published research findings obtained from data collected in this trial. Each publication will be accompanied by a dedicated compendium containing deidentified individual patient data necessary to independently reproduce the analyses presented in the corresponding publication. Such a compendium also contains information about the computer code that was used to generate figures, tables, and other statistical output. Distribution will be via a data repository following FAIR principles (such as zenodo.org).
• IPD Sharing Time Frame: At the time of publication
• IPD Sharing Access Criteria: Access will be provided without limitations. Data will be provided to allow independent computational reproducibility of already published results.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No