Tranexamic Acid in Adherent Placenta (TAP)

Tranexamic Acid in Adherent Placenta (TAP), a Randomized Clinical Trial

The objective of this study is to investigate the effect of tranexamic acid (TXA) administration on the outcome of cesarean-hysterectomy in women with suspected Morbidly Adherent Placenta (MAP; placenta accreta, increta, percreta).

Study Overview

• Status: Withdrawn
• Conditions: Placenta Accreta
• Intervention / Treatment: Drug: Tranexamic Acid (TXA); Drug: Sodium Chloride 0.9%

Detailed Description

This trial is a randomized, double blind, placebo controlled trial to quantify the effects of the preoperative administration of tranexamic acid on estimated blood loss and blood product utilization in women undergoing cesarean-hysterectomy for suspected MAP. Subgroup analyses will be performed for laboratory results (coagulation studies, electrolytes, complete blood count), urine output, hemodynamic parameters, return to OR for continued bleeding, post-operative complications (thromboembolism, wound separation, infection, fever), and length of hospital stay. Eligible patients will be randomized to receive either TXA or placebo.

Women eligible for inclusion will be identified during their prenatal course or on admission to the hospital prior to surgery. They will be offered participation in the study after appropriate counseling regarding the equipoise regarding TXA and its use in pregnancy, and following a question and answer period they will be consented, and assigned a study number.

A randomization table will be generated by the Texas Children's Hospital Investigational Pharmacy, using balanced blocks of 8, and will maintain control of the randomization to ensure blinding of participants and the clinical investigators. Randomization will occur when an order for study medication will be sent on a paper requisition to the Texas Children's Hospital Investigational Pharmacy, and a randomization number will be assigned to correspond to the study number. Ideally, this order will be sumbitted 24h prior to scheduled surgery, but may be submitted for urgent cases by calling the Texas Children's Clinical Pharmacy, and delivering the paper requisition to the 7th Floor Main Pharmacy.

The Investigational Pharmacy will prepare study medication (Tranexamic acid I.V. or Normal saline as placebo) as determined by the randomization. The medication (whether study medication or placebo) will be packaged in identical syringes. Sealed, opaque envelopes will be available to the PI or an assigned designee to permit unblinding (linking randomization number and study number) only in the event of a clinical emergency involving a study partipant during times at which the Investigational Pharmacy is closed (nights, weekends, holidays).

Once a patient has been randomized, the outcome in hospital will be collected even if the study medication is interrupted or not actually given.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 62 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Ultrasound and/or MRI diagnosed MAPL pregnancy scheduled to have a cesarean hysterectomy
• The responsible clinician is substantially uncertain as to whether or not to use TXA
• Consent has been given according to approved procedures

Exclusion Criteria:

• Women for whom the responsible clinician considers there is a clear indication for TXA should not be randomized
• Prior known thromboembolic event during pregnancy
• Known contraindication to TXA (prior adverse reaction)
• Patient unable to give adequate consent due to emergent cesarean hysterectomy
• Bleeding prior to incision
• Prior known thromboembolic event
• Women with a history of any acute venous or arterial thrombosis including retinal artery/retinal vein occlusion, cerebrovascular accident, myocardial infarction, deep venous thrombosis, pulmonary embolism
• History of decreased renal function, renal cortical disease, or significant renal tract disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment; Tranexamic acid (TXA) will be compared with matching placebo (sodium chloride 0.9%).	Drug: Tranexamic Acid (TXA); 1g Tranexamic Acid (TXA) will be given at the time of delivery. If in 30 minutes, heavy bleeding continues, a 2nd dose will be administered.; Other Names: Cyklokapron
Placebo Comparator: Control; Matching placebo (sodium chloride 0.9%) will be compared with treatment group	Drug: Sodium Chloride 0.9%; Dose 1: 1 gram - to be administered by intravenous injection at an approximate rate of 1 mL/minute to all randomized women approximately 10 minutes prior to induction of anesthesia Dose 2: 1 gram - If 30 minutes after beginning the cesarean section there is significant bleeding as defined by the need for the transfusion of 4 or more units of blood products, or if there is a rebleed within the 24 hours after the first dose, a second dose may be given. To be administered by intravenous injection at an approximate rate of 1 mL/minute. The trial treatment injections should not be mixed with blood for transfusion, or infusion solutions containing penicillin or mannitol.; Other Names: NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated blood loss (EBL)	Our data from the past 65 cases of MAPL performed by our team over the past 3 years shows a 2500 +/- 500ml mean blood loss with these surgeries. Using pooled estimates of the reduction in blood loss published in the literature, a 30% reduction is a reasonable expectation.	At patient discharge, upon death or 6 weeks (42 days) after randomization, whichever occurs first
Blood product requirements	The administration of a fixed dose is more practicable in this study and we have thus selected a fixed dose of 1 gram of TXA 10 minutes prior to induction of anesthesia, followed by a second dose of 1 gram if heavy bleeding is encountered 30 or more minutes after starting the cesarean section which requires the transfusion of 4 or more units of blood products. This is within the dose range which has been shown to inhibit fibrinolysis and provide hemostatic benefit.	At patient discharge, upon death or 6 weeks (42 days) after randomization, whichever occurs first
Hemoglobin level change post surgery	The level of hemoglobin change will be measured after surgery.	At patient discharge, upon death or 6 weeks (42 days) after randomization, whichever occurs first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thromboembolic events	Data from all thromboembolic events will be documented on CRFs, including but not limited to the amount and severity of events.	From time patient is given treatment up to 12 weeks post-partum.

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Investigators: Principal Investigator: Michael A Belfort, MD, PhD, Baylor College of Medicine; Principal Investigator: Karin A Fox, MD,MEd, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2018
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: December 29, 2014
• First Submitted That Met QC Criteria: December 30, 2014
• First Posted (Estimate): January 1, 2015

Study Record Updates

• Last Update Posted (Actual): August 23, 2018
• Last Update Submitted That Met QC Criteria: August 21, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Tranexamic Acid
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Placenta Diseases; Placenta Accreta; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: H-41847 (Other Identifier: Baylor College of Medicine Institutional Review Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes