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…
ID
Source
Brief title
Condition
- Postpartum and puerperal disorders
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary full trial objective is to determine the efficacy of low-dose ASA
of preventing symptomatic VTE in the first 6 weeks postpartum, compared to
placebo.
Secondary outcome
Secondary objectives include:
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 ATE (ischemic stroke/TIA or myocardial infarction or peripheral
arterial embolism)
9. Postpartum pre-eclampsia
10. All-cause mortality
Background summary
Pulmonary embolism (PE) is the leading cause of maternal mortality in the
developed world, and the morbidity associated with venous thromboembolism (VTE:
PE or deep vein thrombosis) can be significant. Women are at risk of VTE during
pregnancy and postpartum because of venous stasis, vascular damage and
hypercoagulability. It is unknown whether postpartum thromboprophylaxis is
effective at preventing VTE in patients with VTE risk factors.
Previous trials evaluating postpartum low-molecular-weight heparin (LMWH)
prophylaxis use in patients with VTE risk factors have had low recruitment
rates. One major barrier to recruitment is patients* lack of comfort with the
need for daily LMWH injections. The use of an orally administered medication
would almost certainly improve patient acceptance of thromboprophylaxis in the
postpartum period. The direct oral anticoagulants have similar efficacy to LMWH
in non-pregnant populations, but they are contraindicated while breastfeeding
and may increase the risk of vaginal bleeding. Extended aspirin (ASA)
prophylaxis after 5-10 days of anticoagulation was found to be non-inferior at
preventing VTE after major orthopedic surgery, when compared to other
anticoagulants such as LMWH or rivaroxaban (EPCAT, Ann Intern Med 2013;
EPCATII, NEJM 2018)
Low-dose aspirin (ASA) is considered safe in breastfeeding women. In postpartum
women who were taking ASA 81 mg daily (1-8 months postpartum), ASA was
undetectable in breast milk and salicylate was detected at very low levels
(relative infant dose: 0.4%, threshold considered safe: <10%)3. In a
prospective cohort study that evaluated adverse medication effects in
breast-fed infants, there were no adverse effects seen in 15 breast-fed infants
of mothers taking ASA4. The American College of Chest Physician guidelines,
Canadian Cardiovascular Guidelines and American Academy of Pediatrics support
the use of regular low-dose aspirin in breast feeding women, but recommend
against the use of higher ASA doses given the potential for adverse effects.
If ASA is efficacious in preventing postpartum VTE, use of this simple and
cost-effective medication could change practice and save lives around the
world.
Study objective
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.
Study design
Multicentre randomized controlled pilot trial
Intervention
Treatment with aspirin or placebo , 6 weeks postpartum
Study burden and risks
Risk: Adverse events of study treatment
Burden: Two times 15 minutes study visit by telephone
C210 Foothills Medical Centre 1403 29th street NW
Calgary T2N T29
CA
C210 Foothills Medical Centre 1403 29th street NW
Calgary T2N T29
CA
Listed location countries
Age
Inclusion criteria
ONE (or more) First Order Criterion:
1. Known inherited thrombophilia prior to enrolment: Heterozygous factor V
Leiden or
heterozygous prothrombin gene variant or protein C deficiency or protein S
deficiency
2. Antepartum immobilization (strict bedrest) for >=7 days at any time during the
pregnancy
OR TWO (or more) Second Order Criteria:
1. Pre-pregnancy BMI >=30 kg/m2
2. Smoking >=5 cigarettes/day pre-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)
5. Current pregnancy ending in stillbirth (fetal loss >20 weeks gestation)
6. Emergency cesarean birth (emergency = not 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 and documented fever and laboratory
evidence of infection)
9. Postpartum hemorrhage (>1000 mL regardless of delivery mode)
Exclusion criteria
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)
Pilot PARTUM Trial Version 1.5 08Jun2020
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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 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-000619-58-NL |
| CCMO | NL75956.018.21 |