Tranexamic Acid for Prevention of Hemorrhage in Cesarean Delivery

NCT ID: NCT03856164

Last Updated: 2021-01-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-17

Study Completion Date

2020-08-31

Brief Summary

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The investigators prepared a novel study of tranexamic acid (TXA) designed to estimate the quantity of blood loss in women undergoing elective repeat cesarean deliveries. This is the first trial to utilize a prophylactic dose of TXA prior to incision followed by a subsequent prophylactic dose at placental delivery in obstetric patients undergoing scheduled cesareans. The purpose of this study is to quantify blood loss during uncomplicated repeat cesarean deliveries with and without TXA. The central hypothesis is that TXA administration reduces blood loss and fibrinolysis in women undergoing repeat cesarean sections.

Detailed Description

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Obstetric hemorrhage has been identified as a contributory cause for the United States' suboptimal and inequitable outcomes among pregnant women. As such, obstetric hemorrhage has become a formal focus point in a national agenda to improve maternal outcomes. Strategies to identify maternal hypovolemia and treating obstetric hemorrhage are undergoing organized scrutiny in many states including Texas. Tranexamic acid (TXA) treatment is receiving increased emphasis in obstetric care because TXA inhibits fibrinolysis. Increased clot stability offers the possibility of preventing blood loss (prophylaxis) as well as mitigating ongoing hemorrhage. TXA therapy has been principally studied in nonpregnant populations; results of studies in pregnant women have been lacking.

Tranexamic acid is an antifibrinolytic agent that acts as a competitive inhibitor at the lysine binding sites of plasminogen and inhibits the ability of protease plasmin to cleave the fibrin clot. In large randomized controlled trials, it has been reported to be effective in decreasing perioperative blood loss in a variety of circumstances primarily involving trauma patients. Shakur and co-authors in a trial of 20,000 non-pregnant trauma patients reported a significant reduction in all-cause mortality after TXA administration. In another large study (WOMAN Trial), 20,000 pregnant women with hemorrhage were randomized to TXA or placebo. TXA was associated with a significant decrease in death due to bleeding.

Tranexamic acid's role in treating hemorrhage have been widely studied in non-pregnant populations. Studies of TXA in obstetrics are limited. The American College of Obstetricians and Gynecologists believes the data is insufficient to recommend tranexamic acid for prophylaxis.

The investigators designed a randomized placebo-controlled trial comparing TXA dosing prior to incision for cesarean delivery with a repeat dose given at placental delivery. The purpose is to quantify blood loss during uncomplicated repeat cesarean deliveries with and without TXA. The investigators elected to study scheduled elective cesareans because such procedures are at low risk for profound hemorrhage. It is the intent to have a study cohort where the two treatment groups (TXA or placebo) are as comparable as possible, so the efficacy of TXA is not tested in women with highly variable volumes of obstetric hemorrhage.

Conditions

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Post Partum Hemorrhage Fibrinolysis; Hemorrhage Blood Loss

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Tranexamic acid

Tranexamic Acid for intravenous administration.

Group Type ACTIVE_COMPARATOR

Tranexamic Acid

Intervention Type DRUG

Two doses of Tranexamic Acid (1 gram), diluted in 100 cc of normal saline. Administered intravenously at least 10 minutes prior to skin incision and repeated immediately after placental delivery.

Placebo

Normal saline for intravenous administration.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

100 mL of normal saline. Administered intravenously at least 10 minutes prior to skin incision and repeated immediately after placental delivery.

Interventions

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Tranexamic Acid

Two doses of Tranexamic Acid (1 gram), diluted in 100 cc of normal saline. Administered intravenously at least 10 minutes prior to skin incision and repeated immediately after placental delivery.

Intervention Type DRUG

Placebo

100 mL of normal saline. Administered intravenously at least 10 minutes prior to skin incision and repeated immediately after placental delivery.

Intervention Type DRUG

Other Intervention Names

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Cyklokapron Normal Saline

Eligibility Criteria

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Inclusion Criteria

1. Intrauterine pregnancy
2. Age ≥ 18
3. Gestation age ≥ 37 weeks 0 days
4. Scheduled cesarean delivery
5. Second or third cesarean delivery
6. Singleton pregnancy

Exclusion Criteria

1. First cesarean delivery
2. Four or more cesarean deliveries
3. Intrauterine fetal death
4. Fetal anomalies
5. Documented coagulopathy (Elevated Prothrombin Time (PT), Elevated Partial Thromboplastin Time (PTT), Elevated International Normalized Ratio (INR))
6. Thrombocytopenia (Platelet count \< 100k)
7. Internal bleeding, external bleeding, easy bruising
8. History of thrombotic event
9. Hypertension
10. Diagnosis of renal insufficiency (Creatinine\> 1 mg/dL)
11. Insulin-treated diabetes
12. Suspected morbidly adherent placenta
13. Placenta previa
14. Multiple Gestations
15. BMI ≥ 50
16. Hematocrit ≤ 25
17. Blood transfusion within 24 hours prior to cesarean delivery
18. History of abnormal bleeding or blood disorder
19. Planned general anesthesia
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of Texas Southwestern Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Olutoyosi Ogunkua, MD

Assistant Professor of Anesthesiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Olutoyosi Ogunkua, M.D.

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern

Locations

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Parkland Hospital

Dallas, Texas, United States

Site Status

Countries

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United States

References

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American Society of Anesthesiologists Task Force on Perioperative Blood Management. Practice guidelines for perioperative blood management: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Management*. Anesthesiology. 2015 Feb;122(2):241-75. doi: 10.1097/ALN.0000000000000463. No abstract available.

Reference Type BACKGROUND
PMID: 25545654 (View on PubMed)

WHO Recommendations for the Prevention and Treatment of Postpartum Haemorrhage. Geneva: World Health Organization; 2012. Available from http://www.ncbi.nlm.nih.gov/books/NBK131942/

Reference Type BACKGROUND
PMID: 23586122 (View on PubMed)

Carroli G, Cuesta C, Abalos E, Gulmezoglu AM. Epidemiology of postpartum haemorrhage: a systematic review. Best Pract Res Clin Obstet Gynaecol. 2008 Dec;22(6):999-1012. doi: 10.1016/j.bpobgyn.2008.08.004. Epub 2008 Sep 25.

Reference Type BACKGROUND
PMID: 18819848 (View on PubMed)

GBD 2015 Maternal Mortality Collaborators. Global, regional, and national levels of maternal mortality, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016 Oct 8;388(10053):1775-1812. doi: 10.1016/S0140-6736(16)31470-2.

Reference Type BACKGROUND
PMID: 27733286 (View on PubMed)

WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet. 2017 May 27;389(10084):2105-2116. doi: 10.1016/S0140-6736(17)30638-4. Epub 2017 Apr 26.

Reference Type BACKGROUND
PMID: 28456509 (View on PubMed)

Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 183: Postpartum Hemorrhage. Obstet Gynecol. 2017 Oct;130(4):e168-e186. doi: 10.1097/AOG.0000000000002351.

Reference Type BACKGROUND
PMID: 28937571 (View on PubMed)

Ducloy-Bouthors AS, Jeanpierre E, Saidi I, Baptiste AS, Simon E, Lannoy D, Duhamel A, Allorge D, Susen S, Hennart B. TRAnexamic acid in hemorrhagic CESarean section (TRACES) randomized placebo controlled dose-ranging pharmacobiological ancillary trial: study protocol for a randomized controlled trial. Trials. 2018 Mar 1;19(1):149. doi: 10.1186/s13063-017-2421-6.

Reference Type BACKGROUND
PMID: 29490690 (View on PubMed)

Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other indications. Drugs. 1999 Jun;57(6):1005-32. doi: 10.2165/00003495-199957060-00017.

Reference Type BACKGROUND
PMID: 10400410 (View on PubMed)

Hernandez JS, Alexander JM, Sarode R, McIntire DD, Leveno KJ. Calculated blood loss in severe obstetric hemorrhage and its relation to body mass index. Am J Perinatol. 2012 Aug;29(7):557-60. doi: 10.1055/s-0032-1310528. Epub 2012 Apr 11.

Reference Type BACKGROUND
PMID: 22495893 (View on PubMed)

Huissoud C, Carrabin N, Audibert F, Levrat A, Massignon D, Berland M, Rudigoz RC. Bedside assessment of fibrinogen level in postpartum haemorrhage by thrombelastometry. BJOG. 2009 Jul;116(8):1097-102. doi: 10.1111/j.1471-0528.2009.02187.x. Epub 2009 May 12.

Reference Type BACKGROUND
PMID: 19459866 (View on PubMed)

Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006 Apr 1;367(9516):1066-1074. doi: 10.1016/S0140-6736(06)68397-9.

Reference Type BACKGROUND
PMID: 16581405 (View on PubMed)

Main EK, Goffman D, Scavone BM, Low LK, Bingham D, Fontaine PL, Gorlin JB, Lagrew DC, Levy BS; National Partnership for Maternal Safety; Council on Patient Safety in Women's Health Care. National Partnership for Maternal Safety: Consensus Bundle on Obstetric Hemorrhage. Obstet Gynecol. 2015 Jul;126(1):155-62. doi: 10.1097/AOG.0000000000000869.

Reference Type BACKGROUND
PMID: 26241269 (View on PubMed)

McCormack PL. Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis. Drugs. 2012 Mar 26;72(5):585-617. doi: 10.2165/11209070-000000000-00000.

Reference Type BACKGROUND
PMID: 22397329 (View on PubMed)

Molina RL, Pace LE. A Renewed Focus on Maternal Health in the United States. N Engl J Med. 2017 Nov 2;377(18):1705-1707. doi: 10.1056/NEJMp1709473. No abstract available.

Reference Type BACKGROUND
PMID: 29091560 (View on PubMed)

Say L, Chou D, Gemmill A, Tuncalp O, Moller AB, Daniels J, Gulmezoglu AM, Temmerman M, Alkema L. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014 Jun;2(6):e323-33. doi: 10.1016/S2214-109X(14)70227-X. Epub 2014 May 5.

Reference Type BACKGROUND
PMID: 25103301 (View on PubMed)

John M. Eisenberg Center for Clinical Decisions and Communications Science. Management of Postpartum Hemorrhage: Current State of the Evidence. 2016 Jul 12. In: Comparative Effectiveness Review Summary Guides for Clinicians [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2007-. Available from http://www.ncbi.nlm.nih.gov/books/NBK379234/

Reference Type BACKGROUND
PMID: 27512800 (View on PubMed)

Sentilhes L, Winer N, Azria E, Senat MV, Le Ray C, Vardon D, Perrotin F, Desbriere R, Fuchs F, Kayem G, Ducarme G, Doret-Dion M, Huissoud C, Bohec C, Deruelle P, Darsonval A, Chretien JM, Seco A, Daniel V, Deneux-Tharaux C; Groupe de Recherche en Obstetrique et Gynecologie. Tranexamic Acid for the Prevention of Blood Loss after Vaginal Delivery. N Engl J Med. 2018 Aug 23;379(8):731-742. doi: 10.1056/NEJMoa1800942.

Reference Type BACKGROUND
PMID: 30134136 (View on PubMed)

Ogunkua OT, Duryea EL, Nelson DB, Eddins MM, Klucsarits SE, McIntire DD, Leveno KJ. Tranexamic acid for prevention of hemorrhage in elective repeat cesarean delivery-a randomized study. Am J Obstet Gynecol MFM. 2022 Mar;4(2):100573. doi: 10.1016/j.ajogmf.2022.100573. Epub 2022 Jan 15.

Reference Type DERIVED
PMID: 35038612 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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STU-2018-0315

Identifier Type: -

Identifier Source: org_study_id

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