AntiPhospholipid Syndrome Low-molecular-weight Heparin Pregnancy Loss Evaluation: The Pilot Study

Study Overview
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Brief Summary
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The APPLE pilot trial is a feasibility study that is a multicentre, open-label, randomized controlled trial. Pregnant women with antiphospholipid syndrome (APS) and a history of late (≥10 weeks gestation) or recurrent early (2 <10 weeks) pregnancy loss will be recruited. Eligible and consenting subjects will be assigned to one of two study arms: open-label low-molecular-weight heparin (LMWH) prophylaxis until 37 weeks gestation AND low-dose aspirin (ASA) daily until delivery, or open-label low-dose aspirin daily from randomization until delivery.

Detailed Description
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The purpose of this pilot trial is to determine the feasibility of conducting a multicenter randomized full trial evaluating antepartum prophylaxis with ASA versus LMWH/ASA in women with confirmed APS and a history of late or recurrent early pregnancy loss. Given the large sample size needed to adequately power a large multicenter trial that assesses the efficacy of ASA alone versus LMWH/ASA, the investigators first need to determine if it is possible to meet minimum recruitment rates needed for a full multicenter trial. If the pilot feasibility trial is successful, then the secondary outcomes collected will be used in the analysis of the full multicenter trial.

Official Title
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A Pilot Study Assessing the Feasibility of a Randomized Controlled Trial Evaluating Aspirin Versus Low-molecular-weight Heparin (LMWH) and Aspirin in Women With Antiphospholipid Syndrome and Pregnancy Loss

Conditions
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Antiphospholipid Syndrome in Pregnancy, Pregnancy Loss

Intervention / Treatment
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* Drug: Aspirin 81 mg
* Drug: Low-molecular-weight heparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed pregnancy; 18 years or older; Two or more unexplained pregnancy loss before the 10th week of gestation, AND/OR one or more unexplained pregnancy loss at or beyond the 10th week of gestation; One or more APS laboratory criteria present, according to the revised Sapporo criteria; Exclusion Criteria: Greater than 11 weeks +6 days gestational age at time of randomization; Indication(s) for prophylactic or therapeutic-dose anticoagulation; Contraindication to heparin or aspirin; Received 7 or more doses of LMWH; Previous participation in the trial; Geographic inaccessibility; Refused consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible and consenting subjects will be assigned to one of two study arms. Randomization is stratified by 'high-risk' or 'non-high risk' laboratory criteria and the timing of pregnancy loss (late loss or no late loss).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care Arm<br>Open-label low-molecular-weight heparin (LMWH) prophylaxis until 37 weeks gestation AND low-dose aspirin daily until delivery. | Drug: Low-molecular-weight heparin<br>* The LMWH regime will be at the discretion of the treating physician, with a suggested regime as follows: tinzaparin 4,500 IU sc daily until 20 weeks gestation, and then 4,500 IU sc twice daily until 37 weeks gestation.<br>* Other names: LMWH;|
| Experimental: Experimental Arm<br>Open-label low-dose Aspirin 81 mg daily from randomization until delivery. | Drug: Aspirin 81 mg<br>* Aspirin 81 mg po daily in tablet form.<br>* Other names: Acetylsalicylic Acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study Feasibility: Mean Recruitment Rate Per Center Per Month | The primary feasibility outcome of the pilot trial is the mean recruitment rate per center per month. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Essential Documents | Proportion of sites requiring >18 months to obtain all required approvals/contracts from time of delivery of all study documents. | 18 months | 
| Eligibility | Proportion of screened patients who meet eligibility criteria (i.e. patients who meet inclusion criteria and are also eligible based on exclusion criteria). | 24 months | 
| Consent | Proportion of eligible subjects who provide consent. | 24 months | 
| Withdrawals/Loss to Follow-up | Proportion of withdrawals/loss to follow-up among randomized patients. | 24 months | 
| Crossover Rate | Crossover rate between standard of care and experimental study arms. | 52 weeks | 
| Study Drug Compliance | Level of compliance with study drug through patient recall and patient medication diary. | 52 weeks |