Oxytocin Regimen to Prevent Atony and Postpartum Hemorrhage During Vaginal Delivery: 3-arm RCT

Study Overview
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Brief Summary
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This is a double-blind 3-arm randomized clinical trial to determine whether higher dose oxytocin regimens (compared to the standard regimen) reduce the frequency of uterine atony and postpartum hemorrhage after vaginal delivery. Uterine atony is a loss of tone in the uterine musculature which can cause acute postpartum hemorrhage, which is the major cause of maternal mortality worldwide. Oxytocin is routinely administered postpartum in the US and effectively reduces uterine atony. The optimal dose of oxytocin for vaginal delivery is not known.

Detailed Description
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Same as brief summary. Prospective interim monitoring (stopping) rules will be assessed upon recruitment of 2/3rds of the sample size of 1800. Interim review was conducted by a 3-member DSMB in January of 2010 and their recommendations were implemented.

Official Title
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Comparison of the Effectiveness of 3 Different Dose Regimens of Oxytocin in Preventing Uterine Atony and Postpartum Hemorrhage During Vaginal Delivery

Conditions
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Uterine Atony, Postpartum Hemorrhage

Intervention / Treatment
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* Drug: Oxytocin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 24 weeks, viable pregnancy, singleton or twins Exclusion Criteria: No consent Contraindication to oxytocin Antepartum fetal demise Intrapartum use of concentrated oxytocin Planned cesarean DIC or coagulopathy
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oxytocin 10 units/500cc<br>1 dose only for prophylaxis given over 1 hour | Drug: Oxytocin<br>* See arms<br>* Other names: Pitocin;|
| Experimental: Oxytocin 40 units/500cc<br>One dose only given over 1 hour. Per DSMB recommendations, this intermediate arm was stopped Jan 2010. | Drug: Oxytocin<br>* See arms<br>* Other names: Pitocin;|
| Experimental: Oxytocin 80U/500cc<br>1 dose only given over 1 hour | Drug: Oxytocin<br>* See arms<br>* Other names: Pitocin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Uterine Atony or Postpartum Hemorrhage Requiring Medical (Medication or Blood Transfusion), Surgical or Other Interventional Treatment | the number of subjects with any treatment of uterineatony or hemorrhage. | baseline to discharge (2 - 3 days) | 
| Women in Each Group With Risk Factors for Atony or Postpartum Hemorrhage | In a secondary data analysis, a parsimonious set of independent risk factors for atony or postpartum hemorrhage was established: White, Hispanic, or Other (non-Black of African American) race/ethnicity, preeclampsia, or chorioamnionitus. | Initial hospital discharge (2-3 days) | 
| Risk to Using Increasing Doses of Oxytocin Based on Pre-specified Risk Factors | The frequency of the primary study outcome is examined in a subgroup of 939 women with risk factors for atony or postpartum hemorrhage. These risk factors are identified as White, Hispanic, or Other (non-Black or African American) race/ethnicity, chorioamnionitis, and preeclampsia. | baseline to discharge (2-3 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pre- to Post-delivery Hematocrit (%) | change in hematocrit from admission for delivery (baseline) to post-delivery (4 hours-1day postpartum depending on time of delivery) | During delivery hospitalization: Admission hematocrit - post-delivery hematocrit | 
| Number of Participants Experiencing Individual Treatment or Intervention in the Primary Outcome | the number of individuals with each of the component treatments or individual outcomes in the primary composite. | prior to discharge | 
| Number of Participants Experiencing Postpartum Hemorrhage (Clinical Estimate Greater Than 500cc) | the number of individuals with a clinically estimated postpartum blood loss of 500cc or more | Initial hospital discharge (2-3 days) | 
| Number of Subjects With Hospital Stays Greater Than 4 Days | Number of individuals with prolonged hospitalization defined as 4 days or more prior to initial hospital discharge | Initial hospital discharge (2 days or more) | 
| Number of Subjects Requiring Hypotension Warranting Pressor Agent or Fluid Bolus | number of individuals with hypotension leading to administration of a fluid bolus or vasopressor agent (medication given to raise the blood pressure) | Initial hospital discharge (2-3 days or more) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uterine atony, Postpartum hemorrhage, clinical trial, Prophylactic oxytocin