Carbetocin Versus Oxytocin Infusion Plus Tranexamic Acid During Cesarean Section

Study Overview
=================
Brief Summary
-----------------
Purpose to evaluates the effects of oxytocin infusion with or without intravenous tranexamic acid (TA) in comparison with Carbetocin for prevention of postpartum hemorrhage at a cesarean section with one or more risk factor for postpartum hemorrhage.

Detailed Description
-----------------
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). 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. Carbetocin is a long-acting synthetic analog of oxytocin that can be administered as a single-dose injection; intravenously administered carbetocin has a half-life of approximately 40 min. A single intravenous bolus of carbetocin produces a tetanic uterine contraction within 2 min and persists for an average of 60 min following injection. The aim of this study is to compare the effectiveness of combined tranexamic acid (TA) and oxytocin infusion with intravenous carbetocin for prevention of PPH in patients with risk factors during cesarean section.

Official Title
-----------------
Carbetocin Versus Oxytocin Infusion Plus Tranexamic Acid for Prevention of Postpartum Hemorrhage at Cesarean Section: A Double-Blind Randomized Clinical Trial

Conditions
-----------------
Cesarean Section Complications

Intervention / Treatment
-----------------
* Drug: Carbetocin
* Drug: oxytocin
* Drug: TA
* Drug: placebo to carbetocin
* Drug: placebo to TA
* Drug: placebo to oxytocin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women who undergo elective cesarean section with one or more risk factors for PPH were the candidates for participation With fetal macrosomia, polyhydramnios, low insertion of the placenta, multiple gestations, prolonged labor, chorioamnionitis, past history of PPH, diabetes and high parity (5 previous deliveries). Exclusion Criteria: suspected coagulopathy, history of coronary artery disease or hypertension, women with a history of hypersensitivity to carbetocin, TA or oxytocin general anesthesia, and PPH due to causes other than uterine atony.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Double-Blind Randomized Clinical Trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Carbetocin plus placebo to TA and placebo to oxytocin<br>100 μg carbetocin ampoule or separate placebo ampoule was diluted in 10 mL normal saline and administered slowly (over 30-60 s) intravenously by the anesthetist after the birth of the baby plus two placebo ampoules to oxytocin in 500 mL of intravenous solution infusion over 15 min after delivery of the baby plus 2 placebo ampoules to TA in 100 ml saline by slow infusion | Drug: Carbetocin<br>* 100 μg carbetocin ampoule will be diluted in 10 mL normal saline and administered slowly (over 30-60 s) intravenously by the anesthetist after the birth of the baby<br>* Other names: Active Comparator;Drug: placebo to TA<br>* 2 placebo ampoules to TA in 100 ml saline by slow infusion<br>* Other names: placebo comparator;Drug: placebo to oxytocin<br>* two placebo ampoules to oxytocin in 500 mL of intravenous solution infusion over 15 min after delivery of the baby<br>* Other names: placebo comparator;|
| Active Comparator: oxytocin plus TA<br>20 IU oxytocin in 500 mL of intravenous solution infusion over 15 min after delivery of the baby plus 1gm TA in 100ml saline by slow infusion plus placebo ampoule to carbetocin will be diluted in 10 mL normal saline and administered slowly (over 30-60 s) intravenously by the anesthetist after the birth of the baby | Drug: oxytocin<br>* 20 IU oxytocin in 500 mL of intravenous solution infusion over 15 min after delivery of the baby<br>* Other names: Active Comparator;Drug: TA<br>* 2 ampoules of TA in 100 ml saline by slow infusion<br>* Other names: active comparator;Drug: placebo to carbetocin<br>* placebo ampoule to carbetocin will be diluted in 10 mL normal saline and administered slowly (over 30-60 s) intravenously by the anesthetist after the birth of the baby<br>* Other names: placebo comparator;|
| Active Comparator: oxytocin plus placebo to TA and placebo to carbetocin<br>20 IU oxytocin in 500 mL of intravenous solution infusion over 15 min after delivery of the baby plus 2 placebo ampoules to TA in 100 ml saline by slow infusion plus placebo ampoule to carbetocin will be diluted in 10 mL normal saline and administered slowly (over 30-60 s) intravenously by the anesthetist after the birth of the baby | Drug: oxytocin<br>* 20 IU oxytocin in 500 mL of intravenous solution infusion over 15 min after delivery of the baby<br>* Other names: Active Comparator;Drug: placebo to carbetocin<br>* placebo ampoule to carbetocin will be diluted in 10 mL normal saline and administered slowly (over 30-60 s) intravenously by the anesthetist after the birth of the baby<br>* Other names: placebo comparator;Drug: placebo to TA<br>* 2 placebo ampoules to TA in 100 ml saline by slow infusion<br>* Other names: placebo comparator;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of the patient need of additional pharmacological uterotonic. | calculate the number of the patient need of additional pharmacological uterotonic. | 24 hours post operative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| estimation of intraoperative blood loss (ml) | measure Intraoperative blood loss in ml by gravimetric methods | during the operation | 
| amount of postoperative blood loss | measure amount of blood loss post operative in ml by gravimetric methods | 24 hours post operative | 
| number of patient with postpartum hemorrhage | calculation of the number of the patients with blood loss >1000 ml | 24 hours post operative | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cesarean section, tranexamic acid, oxytocin, carbetocin