E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Aspirin in postpartum women at risk of developing venous thromboembolism
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E.1.1.1 | Medical condition in easily understood language |
Aspirin in postpartum women at risk of developing venous thromboembolism |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049909 |
E.1.2 | Term | Venous thromboembolism prophylaxis |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this pilot trial is to determine whether it is feasible to conduct a full multicentre randomized controlled trial (RCT) to determine whether low-dose aspirin (ASA) is efficacious and safe at preventing postpartum venous thromboembolism (VTE) in women at increased risk of VTE, compared to placebo in the first 6 weeks postpartum |
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E.2.2 | Secondary objectives of the trial |
The secondary full trial objectives are: 1. Late symptomatic VTE from 6 weeks to 90 days 2. Superficial vein thrombosis 3. Distal deep vein thrombosis 4. Subsegmental pulmonary embolism 5. Unusual site thrombosis 6. Major bleeding 7. Clinically relevant non-major bleeding 8. Symptomatic arterial thromboembolism (ischemic stroke/TIA or myocardial infarction or peripheral arterial embolism) 9. Postpartum pre-eclampsia 10. All-cause mortality |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
ONE (or more) First Order Criterion: 1. Known inherited thrombophilia diagnosed prior to enrolment. The necessary laboratory results must be available to confirm the diagnosis. Women with one of the following thrombophilias will be eligible for the trial, regardless of family history of VTE: i) Heterozygous factor V Leiden (genotyping result required), or ii) Heterozygous prothrombin gene variant (genotyping result required), or iii) Protein C deficiency (two abnormal and no normal tests based on local laboratory cutoffs), or iv) Protein S deficiency (two abnormal and no normal tests, one of which is done outside of pregnancy/postpartum OR two abnormal tests in pregnancy/postpartum and one abnormal test and no normal tests in a first degree relative, based on local laboratory cutoffs), or 2. Antepartum immobilization (strict bedrest) for ≥7 days. Immobilization is defined as bed rest with 90% of waking hours spent in bed at any time during the antepartum period TWO (or more) Second Order Criteria: 1. Pre-pregnancy BMI ≥30 kg/m2 (when possible, a documented pre-pregnancy height and weight will be used when available) 2. Smoking ≥5 cigarettes/day pre-pregnancy (smoking history is based on prepregnancy history, irrespective of whether they continue or stop smoking during their pregnancy) 3. Previous clinical history of superficial vein thrombosis 4. Pre-eclampsia (SBP ≥140 and/or DBP ≥90 mmHg on at least one occasion and proteinuria of ≥0.3 grams/24 hours or ≥30 mg/mmol on a random urine sample diagnosed during pregnancy) 5. Current pregnancy ending in stillbirth (pregnancy loss >20 weeks gestation) 6. Emergency cesarean birth (emergency = not previously planned) 7. Small-for-gestational-age infant at time of delivery (<3rd percentile adjusted for gestational age and sex using the standardized international INTERGROWTH chart) 8. Postpartum infection (symptoms/signs of infection and documented fever and laboratory evidence of infection with positive blood cultures or an elevated white blood cell count based on local laboratory cutoffs) 9. Postpartum hemorrhage (>1000 mL of blood loss, regardless of delivery mode) |
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E.4 | Principal exclusion criteria |
Women will be excluded from the trial if they have a known increased risk of VTE where there is sufficiently high risk and/or adequate evidence to determine that LMWH or ASA is indicated, based on their physician and/or local investigator, with examples listed below.
The trial exclusion criteria are as listed: 1. More than 48 hours since delivery of the placenta at the time of randomization 2. Received more than 2 doses of LMWH since delivery of the placenta* 3. Need for postpartum LMWH prophylaxis or systemic anticoagulation as judged by their physician and/or local investigator. May include but is not limited to: a. Documented history of provoked or unprovoked VTE b. Mechanical heart valve(s) c. Known antiphospholipid syndrome (APS) (according to the revised Sapporo/Sydney criteria) d. Known high-risk inherited thrombophilia i) Antithrombin deficiency (two abnormal and no normal tests based on local laboratory cutoffs) ii) Homozygous factor V Leiden (genotyping result required) iii) Homozygous prothrombin gene mutation (genotyping result required) iv) Compound heterozygosity factor V Leiden and prothrombin gene mutation (genotyping result required) v) More than 1 thrombophilia: any combination of 2 or more: factor V Leiden, prothrombin gene mutation, protein C deficiency, protein S deficiency, as previously defined. 4. Need for postpartum ASA as judged by their physician and/or local investigator. May include but is not limited to: a. Documented history of myocardial infarction b. Documented history of ischemic stroke or transient ischemic attack (TIA) 5. Contraindication to ASA including**: a. History of known ASA allergy b. Documented history of a gastrointestinal ulcer c. Known platelet count <50 x 109/L at any time during the current pregnancy or postpartum d. Active bleeding at any site, excluding normal vaginal bleeding, at the time of randomization e. Most recent known hemoglobin ≤70 g/L documented during the current pregnancy or postpartum f. Known severe hypertension (SBP >200 mmHg and/or DBP >120 mmHg) during the current pregnancy or postpartum 6. <18 years of age 7. Unable or refused consent *Pneumatic compression devices or graduated compression stockings are not a contraindication to enrolment but will be recorded. **Postpartum non-steroidal anti-inflammatories (NSAID) use is not a contraindication to enrolment but will be recorded. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Occurence of a VTE within 6 weeks postpartum |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
42 days and 90 days postpartum |
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E.5.2 | Secondary end point(s) |
1. Late symptomatic VTE from 6 weeks to 90 days 2. Superficial vein thrombosis 3. Distal deep vein thrombosis 4. Subsegmental pulmonary embolism 5. Unusual site thrombosis 6. Major bleeding 7. Clinically relevant non-major bleeding 8. Symptomatic arterial thromboembolism (ischemic stroke/TIA or myocardial infarction or peripheral arterial embolism) 9. Postpartum pre-eclampsia 10. All-cause mortality |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
42 days and 90 days postpartum |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Denmark |
France |
Ireland |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |