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

Early Phase 1

Terminated

• Conditions: Antiphospholipid Syndrome in Pregnancy; Pregnancy Loss
• Interventions: Drug: Aspirin 81 mg; Drug: Low-molecular-weight heparin

• Registration Number: NCT03100123
• Lead Sponsor: Ottawa Hospital Research Institute

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-02-21
• Study First Submitted QC: 2017-03-28
• Study First Posted: 2017-04-04
• Study Start: 2017-11-06
• Primary Completion: 2019-10-07
• Study Completion: 2019-10-07
• Status Verified: 2020-03
• Results First Submitted: 2020-03-25
• Results First Submitted QC: 2020-03-25
• Last Update Submitted: 2020-03-25
• Results First Posted: 2020-04-08
• Last Update Posted: 2020-04-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 1

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental Arm	Aspirin 81 mg	Open-label low-dose Aspirin 81 mg daily from randomization until delivery.
Standard of Care Arm	Low-molecular-weight heparin	Open-label low-molecular-weight heparin (LMWH) prophylaxis until 37 weeks gestation AND low-dose aspirin daily until delivery.

Primary Outcome Measures

Name	Time	Method
Study Feasibility: Mean Recruitment Rate Per Center Per Month	24 months	The primary feasibility outcome of the pilot trial is the mean recruitment rate per center per month.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Ottawa Hospital Research Institute; 🇨🇦 Ottawa, Ontario, Canada