Tranexamic Acid Plus Buccal Misoprostol on Blood Loss During and After Cesarean Delivery
Condition: Cesarean Section Complications
MeSH terms: Hemorrhage
Study type: Interventional

Summary: 
      Postpartum hemorrhage (PPH) is potentially life-threatening and is a significant contributor
      to maternal mortality and morbidity especially in developing countries.

      The risk of PPH is much higher for women undergoing cesarean delivery (CD). In the majority
      of cases, uterine atony is responsible for the occurrence of excessive bleeding during or
      following childbirth.

      The Millennium Development Goal of reducing the maternal mortality ratio by 75 % by 2015 will
      remain beyond our reach unless we prioritize the prevention and treatment of PPH in
      low-resource countries.

      Consequently, the administration of uterotonic drugs during cesarean section (CS) and in the
      third stage of labor for vaginal delivery has become essential to diminish the risk of PPH
      and improve maternal safety.

      Oxytocin is regarded as the gold standard uterotonic agent but only has a half-life of 4-10
      min; therefore, at cesarean section oxytocin must be administered as a continuous intravenous
      infusion to attain sustained uterotonic activity throughout the surgical procedure and
      immediate postpartum period.

      Misoprostol is a prostaglandin E1 analog proven in several randomized controlled trials to be
      effective in preventing PPH because of its strong uterotonic effects. In addition,
      misoprostol is inexpensive, stable at room temperature, and easy to administer.

      Misoprostol has been broadly studied in the prevention and treatment of PPH after vaginal
      delivery; however, its use in conjunction with CD has not been investigated as much.

      The buccal route is recognized as having the greatest benefit due to its rapid uptake,
      long-acting effect, and greatest bioavailability compared with other routes of misoprostol
      administration.

      Tranexamic acid(TA) is a synthetic analog of the amino acid lysine,10 as an antifibrinolytic
      agent it has roughly eight times the antifibrinolytic activity of an older analog;
      ε-aminocaproic acid.

      The aim of this study was to compare the effectiveness of combined buccal misoprostol and
      intravenous TA with intravenous oxytocin for the prevention of PPH in patients with risk
      factors during cesarean section.
    

Detailed description: 
      Eligible and consenting participants were randomized via a computer-generated random number
      sequence into one of two groups: one group received a pre-prepared sealed and opaque packet
      containing 400 μg of misoprostol (2 tablets of 200 μg), 2 ampoules of TA (1 gm for infusion)
      and separate placebo ampoule (distilled water). The other group received similar packets
      containing two placebo tablets, two placebo ampoules (distilled water) and separate 2
      ampoules of oxytocin (10 IU in each ampoule for infusion) for slow intravenous injection. The
      misoprostol and placebo tablets were similar in size, shape, and color, and ampoules of
      oxytocin will be also similar to placebo. Randomization was done by the investigator
      immediately before transfer to the theater, whereas the preparation of packets and
      confidential record maintenance was done by the labor room nursing staff.

      Study drug administration 400 μg misoprostol (2 tablets of 200 μg) or two placebo tablets
      were given buccally after spinal anesthesia and few minutes before skin incision; then 1 gm
      TA or separate placebo will be diluted in 100 mL normal saline and administered slowly (over
      30-60 s) intravenously before skin incision, in group 2 20 IU oxytocin or placebo ampoules in
      500 mL of intravenous solution infusion over 15 min after delivery of baby.
    

Intervention name(s): Oxytocin; Tranexamic acid plus misoprostol; misoprostol
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 20 IU oxytocin or placebo ampoules in 500 mL of intravenous solution infusion over 15 min after delivery of the baby.plus 2tab placebo buccal plus 110 ml saline by slow infusion; 1 gm TA or separate placebo will be diluted in 100 mL normal saline and administered slowly (over 30-60 s) intravenously by the anesthetist before skin incision,; 400 μg misoprostol (2 tablets of 200 μg) will be give buccally after spinal anesthesia and few minutes before skin incision;
Other intervention name(s): Active Comparator; Active Comparator; Active Comparator
Intervention MeSH terms: Misoprostol; Tranexamic Acid; Oxytocin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: participants will be randomized via a computer-generated random number sequence into one of two groups: one group received a pre-prepared sealed and opaque packet containing 400 μg of misoprostol (2 tablets of 200 μg), 2 ampoules of TA (1 gm for infusion) and separate placebo ampoule (distilled water). The other group received similar packets containing two placebo tablets, two placebo ampoules (distilled water) and separate 2 ampoules of oxytocin (syntocinon; 10 IU in each ampoule for infusion) for slow intravenous injection. The misoprostol and placebo tablets were similar in size, shape, and color, and ampoules of oxytocin was also similar to placebo. Randomization was done by the resident doctors immediately before transfer to theater, whereas preparation of packets and confidential record maintenance was done by the labor room nursing staff.
Study drug administration
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: cesarean section; tranexamic acid; postpartum hemorrhage; buccal misoprostol