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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tranexamic acid | Active Comparator | Tranexamic Acid for intravenous administration. |
|
| Placebo | Placebo Comparator | Normal saline for intravenous administration. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tranexamic Acid | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Blood Volume Loss | Total blood volume loss will be calculated in milliliters. | 24 hours postpartum. |
| Measure | Description | Time Frame |
|---|---|---|
| D-Dimer (µg/mL) | Measured from blood sample collection. | Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum. |
| Fibrinogen (mg/dL) | Measured from blood sample collection. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Olutoyosi Ogunkua, M.D. | UT Southwestern | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Parkland Hospital | Dallas | Texas | 75235 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25545654 | Background | 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. | |
| 23586122 |
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Of the 110 enrolled participants, all met inclusion criteria and were randomized.
Participants were recruited based on admission for delivery at an academic center between June 2019 and January 2020. The first participant was enrolled on June 17, 2019, and the last participant was enrolled on January 10, 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tranexamic Acid | Participants received two doses (1 gram) of tranexamic acid diluted in 100 mL of normal saline. Tranexamic acid was given intravenously at least 10 minutes prior to skin incision and repeated immediately after placental delivery. |
| FG001 | Placebo | Participants received 100 mL of normal saline. Administered intravenously at least 10 minutes prior to skin incision and repeated immediately after placental delivery. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Tranexamic Acid | Tranexamic Acid for intravenous administration. 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Blood Volume Loss | Total blood volume loss will be calculated in milliliters. | Posted | Mean | Standard Deviation | milliliters | 24 hours postpartum. |
|
During patient admission, minimum of 3 days.
Only serious adverse events were collected according to the study protocol
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tranexamic Acid | Participants received two doses (1 gram) of tranexamic acid diluted in 100 mL of normal saline. Tranexamic acid was given intravenously at least 10 minutes prior to skin incision and repeated immediately after placental delivery. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Olutoyosi Ogunkua | University of Texas Southwestern | 2145578873 | olutoyosi.ogunkua@utsouthwestern.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 13, 2019 | Nov 10, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 13, 2019 | Nov 10, 2020 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 13, 2019 | Nov 10, 2020 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D006473 | Postpartum Hemorrhage |
| D006470 | Hemorrhage |
| ID | Term |
|---|---|
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D014148 | Tranexamic Acid |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D003509 | Cyclohexanecarboxylic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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|
| Placebo | Drug | 100 mL of normal saline. Administered intravenously at least 10 minutes prior to skin incision and repeated immediately after placental delivery. |
|
|
| Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum. |
| Tissue Plasminogen Activator Antigen (ng/mL) | Measured from blood sample collection. | Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum. |
| Plasminogen Activator Inhibitor-Type-1 (Units/mL) | Measured from blood sample collection. | Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum. |
| Rotational Thromboelastometry INTEM and EXTEM Clotting Time | Rotational thromboelastometry is a whole blood viscoelastic test that analyzes deficits in clotting factors, clot strength, and clot breakdown. EXTEM, INTEM, and FIBTEM tests measure the extrinsic pathway, intrinsic pathway, and fibrinogen levels, respectively. Compared to non-pregnant patients, FIBTEM/EXTEM/INTEM amplitudes and the FIBTEM maximum clot firmness are higher in pregnant women. The EXTEM and INTEM clotting time are shorter, indicating the relative hypercoagulability of pregnancy. Reference ranges for INTEM Clotting Time (100-240 seconds), INTEM Maximum Clot Firmness (50-72 millimeter), EXTEM Clotting Time (38-79 seconds), EXTEM Maximum Clot Firmness (50-72 millimeter), FIBTEM Maximum Clot Firmness (9-25 millimeter). | Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum. |
| Rotational Thromboelastometry INTEM, EXTEM, FIBTEM Maximum Clot Firmness | Rotational thromboelastometry is a whole blood viscoelastic test that analyzes deficits in clotting factors, clot strength, and clot breakdown. EXTEM, INTEM, and FIBTEM tests measure the extrinsic pathway, intrinsic pathway, and fibrinogen levels, respectively. Compared to non-pregnant patients, FIBTEM/EXTEM/INTEM amplitudes and the FIBTEM maximum clot firmness are higher in pregnant women. The EXTEM and INTEM clotting time are shorter, indicating the relative hypercoagulability of pregnancy. Reference ranges for INTEM Clotting Time (100-240 seconds), INTEM Maximum Clot Firmness (50-72 millimeter), EXTEM Clotting Time (38-79 seconds), EXTEM Maximum Clot Firmness (50-72 millimeter), FIBTEM Maximum Clot Firmness (9-25 millimeter). | Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum. |
| 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/ |
| 18819848 | Background | 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. |
| 27733286 | Background | 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. |
| 28456509 | Background | 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. |
| 28937571 | Background | Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 183: Postpartum Hemorrhage. Obstet Gynecol. 2017 Oct;130(4):e168-e186. doi: 10.1097/AOG.0000000000002351. |
| 29490690 | Background | 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. |
| 10400410 | Background | 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. |
| 22495893 | Background | 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. |
| 19459866 | Background | 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. |
| 16581405 | Background | 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. |
| 26241269 | Background | 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. |
| 22397329 | Background | 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. |
| 29091560 | Background | 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. |
| 25103301 | Background | 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. |
| 27512800 | Background | 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/ |
| 30134136 | Background | 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. |
| 35038612 | Derived | 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. |
| Placebo |
Normal saline for intravenous administration. Placebo: 100 mL of normal saline. Administered intravenously at least 10 minutes prior to skin incision and repeated immediately after placental delivery. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Parity | Count of Participants | Participants |
|
| Body Mass Index (kg/m^2) | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | D-Dimer (µg/mL) | Measured from blood sample collection. | Posted | Mean | Standard Deviation | µg/mL | Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum. |
|
|
|
| Secondary | Fibrinogen (mg/dL) | Measured from blood sample collection. | Posted | Mean | Standard Deviation | mg/dL | Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum. |
|
|
|
| Secondary | Tissue Plasminogen Activator Antigen (ng/mL) | Measured from blood sample collection. | Posted | Mean | Standard Deviation | ng/mL | Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum. |
|
|
|
| Secondary | Plasminogen Activator Inhibitor-Type-1 (Units/mL) | Measured from blood sample collection. | Posted | Mean | Standard Deviation | IU/mL | Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum. |
|
|
|
| Secondary | Rotational Thromboelastometry INTEM and EXTEM Clotting Time | Rotational thromboelastometry is a whole blood viscoelastic test that analyzes deficits in clotting factors, clot strength, and clot breakdown. EXTEM, INTEM, and FIBTEM tests measure the extrinsic pathway, intrinsic pathway, and fibrinogen levels, respectively. Compared to non-pregnant patients, FIBTEM/EXTEM/INTEM amplitudes and the FIBTEM maximum clot firmness are higher in pregnant women. The EXTEM and INTEM clotting time are shorter, indicating the relative hypercoagulability of pregnancy. Reference ranges for INTEM Clotting Time (100-240 seconds), INTEM Maximum Clot Firmness (50-72 millimeter), EXTEM Clotting Time (38-79 seconds), EXTEM Maximum Clot Firmness (50-72 millimeter), FIBTEM Maximum Clot Firmness (9-25 millimeter). | Posted | Mean | Standard Deviation | seconds | Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum. |
|
|
|
| Secondary | Rotational Thromboelastometry INTEM, EXTEM, FIBTEM Maximum Clot Firmness | Rotational thromboelastometry is a whole blood viscoelastic test that analyzes deficits in clotting factors, clot strength, and clot breakdown. EXTEM, INTEM, and FIBTEM tests measure the extrinsic pathway, intrinsic pathway, and fibrinogen levels, respectively. Compared to non-pregnant patients, FIBTEM/EXTEM/INTEM amplitudes and the FIBTEM maximum clot firmness are higher in pregnant women. The EXTEM and INTEM clotting time are shorter, indicating the relative hypercoagulability of pregnancy. Reference ranges for INTEM Clotting Time (100-240 seconds), INTEM Maximum Clot Firmness (50-72 millimeter), EXTEM Clotting Time (38-79 seconds), EXTEM Maximum Clot Firmness (50-72 millimeter), FIBTEM Maximum Clot Firmness (9-25 millimeter). | Posted | Mean | Standard Deviation | millimeter | Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum. |
|
|
|
| 0 |
| 55 |
| 0 |
| 55 |
| 0 |
| 0 |
| EG001 | Placebo | Participants received 100 mL of normal saline. Administered intravenously at least 10 minutes prior to skin incision and repeated immediately after placental delivery. | 0 | 55 | 0 | 55 | 0 | 0 |
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| D011644 | Puerperal Disorders |
| D014592 | Uterine Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000077324 |
| Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| P.O.D. 1 |
|
| P.O.D. 1 |
|
| P.O.D. 1 |
|
| P.O.D. 1 |
|
| P.O.D. 1 INTEM Clotting Time |
|
| Before Surgery EXTEM Clotting Time |
|
| After Delivery EXTEM Clotting Time |
|
| P.O.D. 1 EXTEM Clotting Time |
|
| P.O.D. 1 INTEM Maximum Clot Firmness |
|
| Before Surgery EXTEM Maximum Clot Firmness |
|
| After Delivery EXTEM Maximum Clot Firmness |
|
| P.O.D. 1 EXTEM Maximum Clot Firmness |
|
| Before Surgery FIBTEM Maximum Clot Firmness |
|
| After Delivery FIBTEM Maximum Clot Firmness |
|
| P.O.D. 1 FIBTEM Maximum Clot Firmness |
|