1 Tranexamic acid for the prevention of postpartum hemorrhage after cesarean delivery: the TRAAP2 trial

Sentilhes, Loïc; Sénat, Marie-Victoire; Lous, Maëla Le; Winer, Norbert; Rozenberg, Patrick; Kayem, Gilles; Verspyck, É.; Fuchs, Florent; Azria, Élie; Gallot, Denis; Korb, Diane; Desbrière, Raoul; Ray, Camille Le; Chauleur, Céline; Marcillac, Fanny de; Perrotin, Franck; Parant, Olivier; Salomon, Laurent; Gauchotte, Émilie; Bretelle, Florence; Bénard, Antoine; Georget, Aurore; Darsonval, Astrid; Deneux‐Tharaux, Catherine

doi:10.1016/j.ajog.2020.12.103

Cited by 11 publications

(16 citation statements)

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“…Calculated blood loss combines peripartum Hb change and total blood volume. The TRAAP2 trial of TXA for PPH prevention in Caesarean births found a reduction in calculated blood loss ≥1000 ml or transfusion (RR = 0.84, 95% CI 0.75–0.94) [ 24 ]. However, surrogate measures of PPH based on Hb change may lack value to patients and clinical relevance.…”

Section: Discussionmentioning

confidence: 99%

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Postpartum haemorrhage in anaemic women: assessing outcome measures for clinical trials

Brenner

Roberts

Balogun

et al. 2022

Trials

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Background Postpartum haemorrhage (PPH) is a leading cause of maternal mortality worldwide. Maternal anaemia greatly increases the risk of PPH, and over a third of all pregnant women are anaemic. Because anaemia reduces the oxygen-carrying capacity of the blood, anaemic women cannot tolerate the same volume of blood loss as healthy women. Yet the same blood loss threshold is used to define PPH in all women. The lack of an established PPH definition in anaemic women means the most appropriate outcome measures for use in clinical trials are open to question. We used data from the WOMAN-2 trial to examine different definitions of PPH in anaemic women and consider their appropriateness as clinical trial outcome measures. Main body The WOMAN-2 trial is assessing tranexamic acid (TXA) for PPH prevention in women with moderate or severe anaemia at baseline. To obtain an accurate, precise estimate of the treatment effect, outcome measures should be highly specific and reasonably sensitive. Some outcome misclassification is inevitable. Low sensitivity reduces precision, but low specificity biases the effect estimate towards the null. Outcomes should also be related to how patients feel, function, or survive. The primary outcome in the WOMAN-2 trial, a ‘clinical diagnosis of PPH’, is defined as estimated blood loss > 500 ml or any blood loss within 24 h sufficient to compromise haemodynamic stability. To explore the utility of several PPH outcome measures, we analysed blinded data from 4521 participants. For each outcome, we assessed its: (1) frequency, (2) specificity for significant bleeding defined as shock index ≥1.0 and (3) association with fatigue (modified fatigue symptom inventory [MFSI]), physical endurance (six-minute walk test) and breathlessness. A clinical diagnosis of PPH was sufficiently frequent (7%), highly specific for clinical signs of early shock (95% specificity for shock index ≥1) and associated with worse maternal functioning after childbirth. Conclusion Outcome measures in clinical trials of interventions for PPH prevention should facilitate valid and precise estimation of the treatment effect and be important to women. A clinical diagnosis of PPH appears to meet these criteria, making it an appropriate primary outcome for the WOMAN-2 trial. Trial registration ClinicalTrials.gov NCT03475342, registered on 23 March 2018; ISRCTN62396133, registered on 7 December 2017; Pan African Clinical Trial Registry PACTR201909735842379, registered on 18 September 2019.

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Section: Discussionmentioning

confidence: 99%

“…Another way to define PPH is using calculated blood loss (estimated total blood volume × proportional change in peripartum Hb) [ 24 ]. After correcting postpartum Hb for RBC transfusions and fluid resuscitation, 8% of women had calculated blood loss ≥1000 ml.…”

Section: Introductionmentioning

confidence: 99%

Postpartum haemorrhage in anaemic women: assessing outcome measures for clinical trials

Brenner

Roberts

Balogun

et al. 2022

Trials

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“…The TRAAP2 trial of TXA for PPH prevention in Caesarian births found a reduction in calculated blood loss ≥ 1000ml or transfusion (RR = 0.84, 95% CI 0.75-0.94). (24) However, surrogate measures of PPH based on Hb change may lack value to patients and clinical relevance. Of note, we found a non-signi cant increase in ability to exercise among women with PPH de ned using peripartum Hb change.…”

Section: Discussionmentioning

confidence: 99%

“…Another way to de ne PPH is using calculated blood loss (estimated total blood volume x proportional change in peripartum Hb). (24) After correcting postpartum Hb for RBC transfusions and uid resuscitation, 8% of women had calculated blood loss ≥1000ml. When compared against shock index ≥1, this outcome had 93% speci city, or a 7% false positive rate (see table 2).…”

Section: Calculated Blood Loss ≥1000mlmentioning

confidence: 99%

Postpartum Haemorrhage in Anaemic Women: Assessing Outcome Measures for Clinical Trials

Brenner¹,

Roberts²,

Balogun³

et al. 2021

Preprint

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Background: Post-partum haemorrhage (PPH) is a leading cause of maternal mortality worldwide. Maternal anaemia greatly increases the risk of PPH and over a third of all pregnant women are anaemic. Because anaemia reduces the oxygen-carrying capacity of the blood, anaemic women cannot tolerate the same volume of blood loss as healthy women. Yet the same blood loss threshold is used to define PPH in all women. The lack of an established PPH definition in anaemic women means the most appropriate outcome measures for use in clinical trials are open to question. We used data from the WOMAN-2 trial to examine different definitions of PPH in anaemic women and consider their appropriateness as clinical trial outcome measures. Main body: The WOMAN-2 trial is assessing tranexamic acid (TXA) for PPH prevention in women with moderate or severe anaemia at baseline. To obtain an accurate, precise estimate of the treatment effect, outcome measures should be highly specific and reasonably sensitive. Some outcome misclassification is inevitable. Low sensitivity reduces precision, but low specificity biases the effect estimate towards the null. Outcomes should also be related to how patients feel, function, or survive. The primary outcome in the WOMAN-2 trial, a ‘clinical diagnosis of PPH’, is defined as estimated blood loss >500 ml or any blood loss within 24 hours sufficient to compromise haemodynamic stability. To explore the utility of several PPH outcome measures, we analysed blinded data from 4,521 participants. For each outcome, we assessed its: 1) frequency, 2) specificity for significant bleeding defined as shock index ≥1.0, and 3) association with fatigue (modified fatigue symptom inventory [MFSI]), physical endurance (six-minute walk test) and breathlessness. A clinical diagnosis of PPH was sufficiently frequent (7%), highly specific for clinical signs of early shock (95% specificity for shock index ≥1) and associated with worse maternal functioning after childbirth.Conclusion: Outcome measures in clinical trials of interventions for PPH prevention should facilitate valid and precise estimation of the treatment effect and be important to women. A clinical diagnosis of PPH appears to meet these criteria, making it an appropriate primary outcome for the WOMAN-2 trial.Clinical trial registration: ClinicalTrials.gov NCT03475342, registered on 23 March 2018; ISRCTN62396133, registered on 7 December 2017; Pan African Clinical Trial Registry PACTR201909735842379, registered on 18 September 2019.

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“…25 This trial showed that TXA treatment resulted in a significant decrease of the primary outcome-PPH defined as a calculated estimated blood loss >1,000 mL or needs for transfusion by day 2-but did not reduce hemorrhagerelated secondary clinical outcomes. 26 Consequently, the place of TXA in PPH prevention after cesarean delivery remains debatable. 27 Documenting the biological effect of TXA on fibrinolytic mediators would add a useful piece of knowledge in this debate, but such investigation has not been conducted so far in the context of prophylactic administration after childbirth.…”

Section: Introductionmentioning

confidence: 99%

Hemostatic Effects of Tranexamic Acid in Cesarean Delivery: An Ancillary Study of the TRAAP2 Study

et al. 2022

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Background Fibrinolysis activation during delivery contributes to postpartum hemorrhage (PPH). Clot lysis time studied with the global fibrinolytic capacity device (GFC/LT) is a functional test which rapidly assesses fibrinolytic profile. Tranexamic acid (TXA) is an efficient antifibrinolytic therapy. Methods We prospectively studied fibrinolysis and coagulation in 33 women included in the TRAAP2 trial, which aimed to assess the impact of TXA in preventing PPH following a cesarean delivery. TXA or placebo was randomly administered after childbirth as part of the TRAAP2 trial's protocol. Fibrinolytic (GFC/LT, plasma concentration of fibrinolysis activators and inhibitors) and hemostatic parameters were assayed at three sample times (TREF [T-reference] after anesthesia, T15 and T120minutes after TXA, or placebo administration). Results All cesarean deliveries were elective. In the placebo group, the clot lysis time assessed with GFC/LT significantly decreased between TREF and T120, indicating an activated fibrinolysis (44 [interquartile range, IQR: 40–48] vs. 34 [IQR: 30–36] minutes, p<0.001). In both TXA and placebo groups, significant fluctuations of the plasmatic concentrations of fibrinolytic mediators were noticed over time, suggesting fibrinolysis activation. Clot lysis time measured by GFC/LT was significantly increased in women of the TXA group as compared with those in the placebo group at T15 (120 [120–120] vs. 36 [34–41] minutes, p<0.001) and T120minutes (113 [99–120] vs. 34 [30–36] minutes, p<0.001) after drug administration, indicating a decreased in fibrinolysis in those women. Conclusions GFC/LT evidenced fibrinolysis activation during cesarean delivery, linked to a decrease in fibrinolytic inhibitors. GFC/LT revealed a significant antifibrinolytic effect of TXA compared with placebo.

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1 Tranexamic acid for the prevention of postpartum hemorrhage after cesarean delivery: the TRAAP2 trial

Cited by 11 publications

References 0 publications

Postpartum haemorrhage in anaemic women: assessing outcome measures for clinical trials

Postpartum haemorrhage in anaemic women: assessing outcome measures for clinical trials

Postpartum Haemorrhage in Anaemic Women: Assessing Outcome Measures for Clinical Trials

Hemostatic Effects of Tranexamic Acid in Cesarean Delivery: An Ancillary Study of the TRAAP2 Study

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