Tranexamic Acid Plus Buccal Misoprostol on Blood Loss During and After Cesarean Delivery

Sponsor

Aswan University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT03710304

Collaborator

(none)

400

Enrollment

Location

Arms

Actual Duration (Months)

21.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Cesarean Section Complications	Drug: Oxytocin Drug: Tranexamic acid plus misoprostol Drug: misoprostol	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

400 participants

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 administrationparticipants 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)

Masking Description:

The trial will be appropriately blinded; the participants, outcome assessors and the surgeon performing the procedure will be blinded to the medication type, which will be used.

Primary Purpose:

Prevention

Official Title:

The Effect of IV Tranexamic Acid Plus Buccal Misoprostol on Blood Loss During and After Cesarean Delivery: a Randomized Controlled Trial

Actual Study Start Date :

Nov 1, 2018

Actual Primary Completion Date :

Mar 31, 2020

Actual Study Completion Date :

Jun 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: oxytocin 20 IU oxytocin ampoules in 500 mL of intravenous solution infusion over 15 min after delivery of the baby.plus 2tab placebo buccal(ranitidine) plus 110 ml saline iv	Drug: Oxytocin 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 Other Names: Active Comparator
Active Comparator: Tranexamic acid plus misoprostol 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 will be diluted in 100 mL normal saline and administered slowly (over 30-60 s) intravenously by the anesthetist before skin incision, plus 500 ml normal saline intravenous solution infusion over 15 min after delivery of the baby	Drug: Tranexamic acid plus misoprostol 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, Other Names: Active Comparator Drug: misoprostol 400 μg misoprostol (2 tablets of 200 μg) will be give buccally after spinal anesthesia and few minutes before skin incision; Other Names: Active Comparator

Arm

Intervention/Treatment

Active Comparator: oxytocin

20 IU oxytocin ampoules in 500 mL of intravenous solution infusion over 15 min after delivery of the baby.plus 2tab placebo buccal(ranitidine) plus 110 ml saline iv

Drug: Oxytocin

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

Other Names:

Active Comparator

Active Comparator: Tranexamic acid plus misoprostol

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 will be diluted in 100 mL normal saline and administered slowly (over 30-60 s) intravenously by the anesthetist before skin incision, plus 500 ml normal saline intravenous solution infusion over 15 min after delivery of the baby

Drug: Tranexamic acid plus misoprostol

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,

Other Names:

Active Comparator

Drug: misoprostol

400 μg misoprostol (2 tablets of 200 μg) will be give buccally after spinal anesthesia and few minutes before skin incision;

Other Names:

Active Comparator

Outcome Measures

Primary Outcome Measures

number of participant required of additional pharmacological uterotonic. [24 hours post operative]
the number of participant need for extra uterotonic drug

Secondary Outcome Measures

difference between preoperative and postoperative hemoglobin [24 hours post operative]
compare of hemoglobin in gm/dl preoperative and 24 hours post operative
intraoperative blood loss [during the operation]
amount of blood loss during the operation
post operative blood loss [24 hours post operative]
amount of blood loss from the end of operation till 24 hours post operative