Dataset Information

TRAAP2 - TRAnexamic Acid for Preventing postpartum hemorrhage after cesarean delivery: a multicenter randomized, doubleblind, placebo- controlled trial - a study protocol.

ABSTRACT: BACKGROUND:An antifibrinolytic agent that blocks lysine-binding sites on plasminogen molecules, tranexamic acid reduces bleeding-related mortality in women with postpartum hemorrhage (PPH), especially administered fairly soon after delivery. According to the randomized controlled trials thus far reported for PPH prevention after cesarean deliveries (n?=?16), women who received tranexamic acid had significantly less postpartum blood loss and no increase in severe adverse effects. These were, however, primarily small single-center studies that had fundamental methodological flaws. Multicenter randomized controlled trials with adequate power are necessary to demonstrate its value persuasively before tranexamic acid goes into widespread use for the prevention of PPH after cesarean deliveries. METHODS/DESIGN:This study will be a multicenter, double-blind, randomized controlled trial with two parallel groups including 4524 women with cesarean deliveries before or during labor, at a term ?34?weeks, modeled on our previous study of tranexamic acid administered after vaginal deliveries. Treatment (either tranexamic acid 1?g or placebo) will be administered intravenously just after birth. All women will also receive a prophylactic uterotonic agent. The primary outcome will be the incidence of PPH, defined by a calculated estimated blood loss >?1000?mL or a red blood cell transfusion before day 2 postpartum. This study will have 80% power to show a 20% reduction in the incidence of PPH, from 15.0 to 12.0%. DISCUSSION:As an, inexpensive, easy to administer drug that can be add to the routine management of cesarean births in delivery rooms, tranexamic acid is a promising candidate for preventing PPH after these births. This large, adequately powered, multicenter randomized placebo-controlled trial seeks to determine if the benefits of the routine prophylactic use of tranexamic acid after cesarean delivery significantly outweigh its risks. TRIAL REGISTRATION:ClinicalTrials.gov NCT03431805 (February 12, 2018).

SUBMITTER: Sentilhes L

PROVIDER: S-EPMC6995226 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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TRAAP2 - TRAnexamic Acid for Preventing postpartum hemorrhage after cesarean delivery: a multicenter randomized, doubleblind, placebo- controlled trial - a study protocol.

Sentilhes Loïc L Daniel Valérie V Deneux-Tharaux Catherine C

BMC pregnancy and childbirth 20200131 1

<h4>Background</h4>An antifibrinolytic agent that blocks lysine-binding sites on plasminogen molecules, tranexamic acid reduces bleeding-related mortality in women with postpartum hemorrhage (PPH), especially administered fairly soon after delivery. According to the randomized controlled trials thus far reported for PPH prevention after cesarean deliveries (n = 16), women who received tranexamic acid had significantly less postpartum blood loss and no increase in severe adverse effects. These we ...[more]

PMID: 32005192

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Project description:Postpartum hemorrhage (PPH) is a major cause of maternal mortality, accounting for one quarter of all maternal deaths worldwide. Estimates of its incidence in the literature vary widely, from 3 % to 15 % of deliveries. Uterotonics after birth are the only intervention that has been shown to be effective in preventing PPH. Tranexamic acid (TXA), an antifibrinolytic agent, has been investigated as a potentially useful complement to uterotonics for prevention because it has been proved to reduce blood loss in elective surgery, bleeding in trauma patients, and menstrual blood loss. Randomized controlled trials for PPH prevention after cesarean (n = 10) and vaginal (n = 2) deliveries show that women who received TXA had significantly less postpartum blood loss without any increase in their rate of severe adverse effects. However, the quality of these trials was poor and they were not designed to test the effect of TXA on the reduction of PPH incidence. Large, adequately powered, multicenter randomized controlled trials are required before the widespread use of TXA to prevent PPH can be recommended.A multicenter, double-blind, randomized controlled trial will be performed. It will involve 4000 women in labor for a planned vaginal singleton delivery, at a term ? 35 weeks. Treatment (either TXA 1 g or placebo) will be administered intravenously just after birth. Prophylactic oxytocin will be administered to all women. The primary outcome will be the incidence of PPH, defined by blood loss ?500 mL, measured with a graduated collector bag. This study will have 80 % power to show a 30 % reduction in the incidence of PPH, from 10.0 % to 7.0 %.In addition to prophylactic uterotonic administration, a complementary component of the management of third stage of labor acting on the coagulation process may be useful in preventing PPH. TXA is a promising candidate drug, inexpensive, easy to administer, and simple to add to the routine management of deliveries in hospitals. This large, adequately powered, multicenter, randomized placebo-controlled trial seeks to determine if the risk-benefit ratio favors the routine use of TXA after delivery to prevent PPH.ClinicalTrials.gov NCT02302456 (November 17, 2014).

Project description:Women who undergo intrapartum caesarean delivery (CD) are at increased risk of postpartum hemorrhage (PPH) compared with those undergoing prelabor CD. To determine whether the presence and strength of the associations between individual risk factors and severe PPH vary among women undergoing prelabor CD or intrapartum CD, stratified analyses are needed according to CD subtype.To identify risk factors for severe PPH within 2 distinct CD populations, prelabor CD and intrapartum CD, we performed 2 case-control studies. Women in each study cohort delivered at a tertiary obstetric center in the United States between 2002 and 2012. For each study, cases were women who had a blood loss ?1500 mL or who received an intraoperative or postoperative transfusion up to 48 hours after delivery. Risk factors for severe PPH among women undergoing prelabor CD or intrapartum CD were examined in separate logistic regression models.For prelabor CD, we identified 269 cases and 550 controls. Clinical factors with the highest adjusted odds for severe PPH during prelabor CD were general anesthesia (adjusted odds ratio [aOR] = 22.3; 95% confidence interval [CI], 4.9-99.9; reference group = spinal anesthesia), multiple pregnancies (aOR = 8.0; 95% CI, 4.2-15.0; reference group = singleton pregnancy), and placenta previa (aOR = 6.3; 95% CI, 3.4-11.8). For intrapartum CD, we identified 278 cases and 572 controls. Clinical factors with the highest adjusted odds for severe PPH during intrapartum CD were general anesthesia (aOR = 5.4; 95% CI, 1.7-17.1), multiple pregnancies (aOR = 3.2; 95% CI, 1.7-6.3), and a predelivery hemoglobin ? 9.9 g/dL (aOR = 3.0; 95% CI, 1.3-6.9; reference group = predelivery hemoglobin ? 11 g/dL).Women who undergo prelabor CD and intrapartum CD have several shared risk factors for severe PPH (general anesthesia and multiple pregnancies). However, the risk factor profiles for severe PPH differed between these CD cohorts. Recognizing these differences may be important when planning resources and interventions for high-risk patients undergoing either prelabor or intrapartum CD.

Project description:BACKGROUND:Evidence increases that a high or a standard dose of tranexamic acid (TA) reduces postpartum bleeding. The TRACES pharmacobiological substudy aims to establish a therapeutic strategy in hemorrhagic (H) Cesarean section (CS) with respect to the intensity of fibrinolysis by using innovative assays. METHOD/DESIGN:The TRACES trial is a multicenter, randomized, double-blind, placebo-controlled, TA dose-ranging study that measures simultaneously plasmatic and uterine and urine TA concentrations and the plasmin peak inhibition tested by a simultaneous thrombin plasmin generation assay described by Van Geffen (novel hemostasis assay [NHA]). Patients undergoing H CS (>800 mL) will receive blindly TA 0.5 g or 1 g or placebo. A non-hemorrhagic (NH) group will be recruited to establish plasmin generation profile. Venous blood will be sampled before, at the end, and then at 30, 60, 120, and 360 min after injection. Uterine bleeding will be sampled after injection. Urine will be sampled 2 h and 6 h after injection. The number of patients entered into the study will be 114 H?+?48 NH out of the 390 patients of the TRACES clinical trial. DISCUSSION:To explore the two innovative assays, a preliminary pilot study was conducted. Blood samples were performed repeatedly in patients undergoing either a H (>800 mL) or NH (<800 mL) CS and in non-pregnant women (NP). H patients received TA (0-2 g). Dose-dependent TA plasmatic concentrations were determined by LC-MS/MS quantification. Plasmin generation and its inhibition were tested in vitro and in vivo using the simultaneous thrombin-plasmin generation assay (STPGA). The pilot study included 15 patients in the H group, ten patients in the NH group, and seven patients in the NP group. TA plasmatic concentration showed a dose-dependent variation. STPGA inter-assay variation coefficients were?<?20% for all plasmin parameters. Inter-individual dispersion of plasmin generation capacity was higher in H and NH groups than in NP group. Profile evolution over time was different between groups. This preliminary technical validation study allows TRACES pharmacobiological trial to be conducted. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02797119. Registered on 13 June 2016.

Project description:BackgroundEvidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH.MethodsWe performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis.ResultsBetween December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P=0.40). There was a signal for interaction with onset-to-treatment time (Pinteraction=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P=0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P=0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation.ConclusionsIn a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH.RegistrationURL: https://clinicaltrials.gov; Unique identifier: NCT02866838.

Project description:BACKGROUND:Postpartum haemorrhage (PPH) is responsible for about 100,000 maternal deaths every year, most of which occur in low- and middle-income countries. Tranexamic acid (TXA) reduces bleeding by inhibiting the enzymatic breakdown of fibrin blood clots. TXA decreases blood loss in surgery and reduces death due to bleeding after trauma. When given within 3 h of birth, TXA reduces deaths due to bleeding in women with PPH. However, for many women, treatment of PPH is too late to prevent death. Over one third of pregnant women in the world are anaemic and many are severely anaemic. These women have an increased risk of PPH and suffer more severe outcomes if PPH occurs. There is an urgent need to identify a safe and effective way to reduce postpartum bleeding in anaemic women. METHODS/DESIGN:The WOMAN-2 trial is an international, multicentre, randomised, double-blind, placebo-controlled trial to quantify the effects of TXA on postpartum bleeding in women with moderate or severe anaemia. Ten thousand women with moderate or severe anaemia who have given birth vaginally will be randomised to receive 1?g of TXA or matching placebo by intravenous injection immediately (within 15?min) after the umbilical cord is cut or clamped. The primary outcome is the proportion of women with a clinical diagnosis of primary PPH. The cause of PPH will be described. Data on maternal health and wellbeing, maternal blood loss and its consequences, and other health outcomes will be collected as secondary outcomes. The main analyses will be on an 'intention-to-treat' basis, irrespective of whether the allocated treatment was received. Results will be presented as appropriate effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses will be based on the severity of anaemia (moderate versus severe) and type of labour (induced or augmented versus spontaneous). A study with 10,000 patients will have over 90% power to detect a 25% relative reduction from 10 to 7.5% in PPH. The trial will be conducted in hospitals in Africa and Asia. DISCUSSION:The WOMAN-2 trial should provide reliable evidence for the effects of TXA for preventing postpartum bleeding in women with anaemia. TRIAL REGISTRATION:ISRCTN, ISRCTN62396133 . Registered on 7 December 2017; ClincalTrials.gov, ID: NCT03475342 . Registered on 23 March 2018.

Dataset Information

TRAAP2 - TRAnexamic Acid for Preventing postpartum hemorrhage after cesarean delivery: a multicenter randomized, doubleblind, placebo- controlled trial - a study protocol.

Publications

TRAAP2 - TRAnexamic Acid for Preventing postpartum hemorrhage after cesarean delivery: a multicenter randomized, doubleblind, placebo- controlled trial - a study protocol.

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