Prophylactic Tranexamic Acid Reduces Postpartum Hemorrhage

Phase 4

Recruiting

• Conditions: Postpartum Hemorrhage; Systemic Autoimmune Diseases
• Interventions: Drug: tranexamic acid; Drug: normal saline

• Registration Number: NCT06754371
• Lead Sponsor: RenJi Hospital

Brief Summary

Postpartum hemorrhage (PPH) is the most significant leading cause of pregnancy-related mortality in high-risk cesarean delivery women. Systemic autoimmune diseases are associated with adverse pregnancy outcomes (APOs), including PPH, preeclampsia, thromboembolism, abortion, and intrauterine growth restriction. The incidence of PPH in women with systemic lupus erythematosus has been reported to be as high as 34%. Prevention of PPH is the key to reduce complications in high-risk women. In recent years, a large number of clinical studies have confirmed that the early preventive use of tranexamic acid(TXA) can reduce the amount of blood loss, the need for additional uterine contraction agents, the risk of blood transfusion, and maternal adverse outcomes, and do not increase the risk of thromboembolic events, which can be used to prevent PPH. However, the study population of TXA is mainly low-risk puerpera, and there is still a lack of relevant research on TXA used in pregnant women with systemic autoimmune diseases. The purpose of this study was to evaluate the safety and efficacy of TXA in preventing postpartum hemorrhage after cesarean delivery in women with systemic autoimmune disease, as well as the maternal and neonatal risks associated with systemic autoimmune disease, to provide evidence for clinical practice and further research.

Detailed Description

The worldwide estimated cumulative prevalence of autoimmune disease is approximately 5%. Studies are often limited by small sample sizes and focused on a specific autoimmune disease such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), which is characterized by the production of autoantibodies leading to inflammation of multiple organs. Systemic autoimmune diseases are associated with adverse pregnancy outcomes (APOs), including increased cesarean delivery rates, PPH, preeclampsia, thromboembolism, abortion, premature delivery, and intrauterine growth restriction. Preeclampsia is the most commonly reported complication in patients with SLE and is also a high risk factor for PPH. The incidence of PPH in women with SLE has been reported to be as high as 34%. PPH increases the need for blood transfusion and related complications and is a significant clinical and socio-economic problem. Therefore, prevention of PPH is the key to reduce the postpartum complications of high-risk women. At present, the methods commonly used to prevent PPH after cesarean delivery include uterine massage, prophylactic use of uterine contraction agents in the third stage of labor, and early use of TXA. Recent clinical studies of TXA use in high-risk cesarean delivery women have shown that prophylactic use of TXA significantly reduces blood loss, prevents PPH, and reduces ICU admission and length of stay. There was no evidence of an increased risk of maternal-related complications with TXA use. But there is still a lack of relevant research on TXA used in pregnant women with systemic autoimmune diseases. Anti-phospholipid antibodies (aPL) are often present in SLE and APS patients, which predict serious perinatal complications and are associated with the risk of thrombosis. aPL are detected not only in SLE and APS but also in other connective tissue diseases such as systemic sclerosis (SSc), Sjögren's syndrome (SS), rheumatoid arthritis (RA), and undifferentiated connective tissue disease (UCTD). Although TXA has been widely used in patients at high risk for thromboembolism, such as trauma, orthopedics, and cardiac surgery in recent years, the evidence strongly supports that it does not increase the risk of death or thromboembolic complications. More evidence from high quality randomized controlled trials is needed to assess the benefits and risks of its use in women at high risk of PPH after cesarean delivery.

The aim of this study was to evaluate the safety and efficacy of TXA in preventing PPH after cesarean delivery in women with systemic autoimmune disease. Patients undergoing cesarean delivery were randomly assigned to TXA group(intravenous infusion of TXA 1g (20ml) 10min before skin dissection) and placebo group(intravenous infusion of normal saline 20ml 10min before skin dissection).The estimated blood loss 24h postoperatively, blood transfusion 3d postpartum, additional uterotonics, other surgical intervention for PPH and thromboembolic events were recorded.

Study Timeline

• Study First Submitted: 2024-12-22
• Study First Submitted QC: 2024-12-22
• Study First Posted: 2024-12-31
• Study Start: 2025-01-06
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-13
• Last Update Posted: 2025-03-17
• Primary Completion: 2027-01
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 276

Inclusion Criteria

1. Patients undergoing cesarean delivery
2. Preoperative diagnosis of pregnancy with systemic autoimmune diseases (systemic lupus erythematosus, antiphospholipid syndrome, systemic sclerosis, Sjogren's syndrome, rheumatoid arthritis, undifferentiated connective tissue disease)
3. Obtain informed consent.

Exclusion Criteria

1. intrauterine fetal death
2. Existing/previous history of thromboembolism
3. Hemorrhagic disease, significant prenatal bleeding
4. Balloon placement of internal iliac artery
5. Allergic to tranexamic acid
6. Severe renal insufficiency (serum creatinine >451μmol/L or blood urea nitrogen >20mmol/L)
7. Epilepsy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tranexamic acid group	tranexamic acid	intravenous infusion of tranexamic acid 1g (20ml) 10min before skin dissection
Placebo group	normal saline	intravenous infusion of normal saline 20ml 10min before skin dissection

Primary Outcome Measures

Name	Time	Method
The incidence of postpartum hemorrhage	From skin incision to 1day after surgery	Postpartum hemorrhage is defined as blood loss of 1000 mL or more within the first 24 h after cesarean delivery.
Estimated blood loss within 1day after surgery	From skin incision to 1day after surgery	Estimated blood loss is calculated by GROSS EQUATION: Estimated Blood Loss (EBL) = EBV ×((HCT1 - HCT2)/(HCT mean)), EBV = Estimated Blood volume; whereas EBV = Patient's weight (in kilogram) × 70 mL/kg, HCT1=preoperative hematocrit, HCT2 = postoperative hematocrit, and HCT mean = (HCT1 + HCT2)/2;

Secondary Outcome Measures

Name	Time	Method
The volume of blood transfusion within 3days after surgery and complications	From skin incision to 3days after surgery	The volume of blood transfusion within 3days after surgery and complications(such as fever, allergy, hemolysis, renal dysfunction，etc）
Whether additional uterotonics are needed	From the delivery of placenta until 3 days postoperatively	Uterotonics other than intraoperative routine dose intravenous and intrauterine infusion of oxytocin.
Whether other surgical intervention for PPH are needed	From the delivery of placenta until 3 days postoperatively	Patients who need other surgical intervention(such as intrauterine balloon compression hemostasis, uterine artery ligation or embolization and hysterectomy) to control PPH
Incidence of thromboembolic events	Patients will be followed up to one week after surgery	The occurrence of thromboembolic events within one week of delivery, including deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke
Maternal complications	Patients will be followed up to 3days after surgery	Occurrence of adverse effects (nausea, vomiting, headache, epilepsy, renal impairment，coagulopathy) within 3days after surgery.
Maternal and neonatal 3 months mortality	Patients and neonates will be followed up to 3 months after surgery	All-cause 3 months mortality
Estimated intraoperative blood loss	From skin incision to the end of the surgery	Estimated intraoperative blood loss is calculated using the formula: collected blood volume in the suction canister (ml)-the volume of amniotic fluid (ml)-the volume of flushing (ml) + the volume from the gauze tampon (ml)

Trial Locations

Locations (1)

Renji Hospital, Shanghai Jiaotong University, School of Medcine; 🇨🇳 Shanghai, Shanghai, China