Clinical trial NCT05340205: Blood Loss During Cesarean Delivery in Placenta Previa Patients
Official title: The Efficacy and Safety of Intrauterine Misoprostol Versus Intravenous Tranexamic Acid in Reducing Blood Loss During and After Cesarean Delivery in Patients With Placenta Previa: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Placenta Previa
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2022-04-22
Enrollment: 81
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: To compare the efficacy and safety profile of intravenous tranexamic acid versus intrauterine misoprostol in reducing the blood loss during and after cesarean delivery in pregnant women diagnosed with placenta previa

Detailed description: Placenta previa is defined as complete or partial covering of the internal os of the cervix with the placenta, at more than 16 weeks of gestation. It affects 0.3% to 2% of pregnancies in the third trimester and has become more evident secondary to the increasing rates of cesarean delivery (CD).

Placenta previa is a major risk factor for postpartum hemorrhage (PPH) and can lead to maternal and neonatal morbidity and mortality. Uncontrolled PPH from placenta previa may necessitate blood transfusion, hysterectomy, admission to the intensive care unit, or even death.

The efficacy of routine administration of oxytocin, to reduce the frequency of PPH after vaginal and cesarean birth is well-established. The Royal College of Obstetricians and Gynecologists recommends a slow IV bolus dose of 5 IU of oxytocin after delivery of the neonate in CD to ensure adequate uterine contractility, reduce intraoperative blood loss and prevent PPH. Likewise, the American College of Obstetricians and Gynecologists recommends the practice to use oxytocin but infusion instead of a bolus dose. Regardless of the mode of administration, oxytocin use in the setting of CD may result in maternal adverse effects, such as hypotension and tachycardia.

Misoprostol, a prostaglandin E1 analogue with strong uterotonic properties binds to myometrial cells to cause strong myometrial contractions. Misoprostol has been suggested as an alternative to injectable uterotonic agents for preventing PPH following vaginal or CD. It can be used orally, sublingually, buccally, rectally or put intrauterine with similar efficacy as oxytocin in reducing blood loss, preventing and treating PPH. Because of its availability, low cost, thermal stability, and ease of administration, misoprostol is suitable for worldwide use even in low resource settings in developing countries.

Tranexamic Acid (TA) is an analogue of lysine that inhibits fibrinolysis by competitively binding to plasminogen. It prevents the lysis of formed clot by inhibiting activation of plasminogen and plasmin. It is ten times more potent than amino-caproic acid. Several studies had assessed the use of TA in both the prophylaxis against and the treatment of PPH with the conclusion that TA reduces the following; blood loss in women with PPH, the need for hysterectomy, the risk of severe anemia and the need for further blood transfusion; hence, this could contribute significantly to the goal of reducing maternal mortality

Eligibility criteria: Inclusion Criteria:

* Parity: primigravida or multigravida.
* Gestational age: ≥ 36 weeks (confirmed by the first day of the last menstrual period or first trimester ultrasound scan).
* Candidate for termination of pregnancy by cesarean delivery.
* Singleton living healthy normally growing fetus.
* Cesarean delivery under spinal anesthesia.
* Pregnancies complicated with placenta previa diagnosed preoperatively by ultrasonography (placenta previa was defined as placenta partially or totally covers the cervix)

Exclusion Criteria:

* Patients diagnosed with morbidly adherent placenta.
* Placenta previa cases requiring cesarean hysterectomy in the primary surgery.
* Patients with preoperative anemia (Hemoglobin \<9 gm/dl).
* History of thromboembolic event.
* Known allergy to tranexamic acid or prostaglandins.
* Bronchial asthma or other contraindications of misoprostol.
* Patients with other risk factors of postpartum hemorrhage (e.g., polyhydramnios, fetal macrosomia, uterine fibroid).
* Patients known to have bleeding tendency (e.g., those receiving anticoagulation, patients with thrombocytopenia, factor VIII or IX deficiency or Von Willebrand's disease).
* More than 2 previous cesarean deliveries procedures.
* Prolonged procedure (more than 2 hours from skin incision to skin closure).
* Concomitant maternal medical disorders (either chronic or pregnancy induced)

Primary outcomes:
measure: To compare the estimated blood loss during cesarean delivery among the three groups
timeFrame: less than 2 hours
Secondary outcomes:
measure: The Use of additional ecbolics denoting uterine atony
timeFrame: Baseline
measure: The occurrence of excessive blood loss (> 1000 mL) within the first 24 hours postoperatively
timeFrame: First 24 hours postoperatively
measure: The need for blood transfusion
timeFrame: During cesarean delivery and the first 24 hours postoperatively
measure: The occurrence of any maternal side effects in the studied groups
timeFrame: First 6 hours postoperatively
measure: The occurrence of any neonatal outcome in the studied groups
timeFrame: The first 6 hours postoperatively
Other outcomes:
Locations:
city: Giza
country: Egypt
facility: Kasralainy Cairo University
Study officials:
affiliation: Cairo University
name: Tarek El Husseiny, MD
role: STUDY_DIRECTOR
References:
citation: Bhattacharya S, Ghosh S, Ray D, Mallik S, Laha A. Oxytocin administration during cesarean delivery: Randomized controlled trial to compare intravenous bolus with intravenous infusion regimen. J Anaesthesiol Clin Pharmacol. 2013 Jan;29(1):32-5. doi: 10.4103/0970-9185.105790.
citation: Martinelli KG, Garcia EM, Santos Neto ETD, Gama SGND. Advanced maternal age and its association with placenta praevia and placental abruption: a meta-analysis. Cad Saude Publica. 2018 Feb 19;34(2):e00206116. doi: 10.1590/0102-311X00206116.
citation: Prata N, Weidert K. Efficacy of misoprostol for the treatment of postpartum hemorrhage: current knowledge and implications for health care planning. Int J Womens Health. 2016 Jul 29;8:341-9. doi: 10.2147/IJWH.S89315. eCollection 2016.
citation: Pabinger I, Fries D, Schochl H, Streif W, Toller W. Tranexamic acid for treatment and prophylaxis of bleeding and hyperfibrinolysis. Wien Klin Wochenschr. 2017 May;129(9-10):303-316. doi: 10.1007/s00508-017-1194-y. Epub 2017 Apr 21.
citation: Sood AK, Singh S. Sublingual misoprostol to reduce blood loss at cesarean delivery. J Obstet Gynaecol India. 2012 Apr;62(2):162-7. doi: 10.1007/s13224-012-0168-2. Epub 2012 Jun 1.
citation: Vogel JP, West HM, Dowswell T. Titrated oral misoprostol for augmenting labour to improve maternal and neonatal outcomes. Cochrane Database Syst Rev. 2013 Sep 23;2013(9):CD010648. doi: 10.1002/14651858.CD010648.pub2.
citation: Della Corte L, Saccone G, Locci M, Carbone L, Raffone A, Giampaolino P, Ciardulli A, Berghella V, Zullo F. Tranexamic acid for treatment of primary postpartum hemorrhage after vaginal delivery: a systematic review and meta-analysis of randomized controlled trials. J Matern Fetal Neonatal Med. 2020 Mar;33(5):869-874. doi: 10.1080/14767058.2018.1500544. Epub 2018 Sep 10.