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

Primary Purpose

Antiphospholipid Syndrome in Pregnancy, Pregnancy Loss

Status
Terminated
Phase
Early Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Aspirin 81 mg
Low-molecular-weight heparin
Sponsored by
Ottawa Hospital Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Antiphospholipid Syndrome in Pregnancy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Ottawa Hospital Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard of Care Arm

Experimental Arm

Arm Description

Open-label low-molecular-weight heparin (LMWH) prophylaxis until 37 weeks gestation AND low-dose aspirin daily until delivery.

Open-label low-dose Aspirin 81 mg daily from randomization until delivery.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
February 21, 2017
Last Updated
March 25, 2020
Sponsor
Ottawa Hospital Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT03100123
Brief Title
AntiPhospholipid Syndrome Low-molecular-weight Heparin Pregnancy Loss Evaluation: The Pilot Study
Acronym
APPLE
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Terminated
Why Stopped
Pilot deemed not feasible by Steering Committee due to recruitment rate.
Study Start Date
November 6, 2017 (Actual)
Primary Completion Date
October 7, 2019 (Actual)
Study Completion Date
October 7, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Antiphospholipid Syndrome in Pregnancy, Pregnancy Loss

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
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)
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard of Care Arm
Arm Type
Active Comparator
Arm Description
Open-label low-molecular-weight heparin (LMWH) prophylaxis until 37 weeks gestation AND low-dose aspirin daily until delivery.
Arm Title
Experimental Arm
Arm Type
Experimental
Arm Description
Open-label low-dose Aspirin 81 mg daily from randomization until delivery.
Intervention Type
Drug
Intervention Name(s)
Aspirin 81 mg
Other Intervention Name(s)
Acetylsalicylic Acid
Intervention Description
Aspirin 81 mg po daily in tablet form.
Intervention Type
Drug
Intervention Name(s)
Low-molecular-weight heparin
Other Intervention Name(s)
Tinzaparin, Dalteparin, Enoxaparin, LMWH
Intervention Description
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.
Primary Outcome Measure Information:
Title
Study Feasibility: Mean Recruitment Rate Per Center Per Month
Description
The primary feasibility outcome of the pilot trial is the mean recruitment rate per center per month.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Essential Documents
Description
Proportion of sites requiring >18 months to obtain all required approvals/contracts from time of delivery of all study documents.
Time Frame
18 months
Title
Eligibility
Description
Proportion of screened patients who meet eligibility criteria (i.e. patients who meet inclusion criteria and are also eligible based on exclusion criteria).
Time Frame
24 months
Title
Consent
Description
Proportion of eligible subjects who provide consent.
Time Frame
24 months
Title
Withdrawals/Loss to Follow-up
Description
Proportion of withdrawals/loss to follow-up among randomized patients.
Time Frame
24 months
Title
Crossover Rate
Description
Crossover rate between standard of care and experimental study arms.
Time Frame
52 weeks
Title
Study Drug Compliance
Description
Level of compliance with study drug through patient recall and patient medication diary.
Time Frame
52 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Rodger, MD
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Leslie Skeith, MD
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ottawa Hospital Research Institute
City
Ottawa
State/Province
Ontario
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32358837
Citation
Hamulyak EN, Scheres LJ, Marijnen MC, Goddijn M, Middeldorp S. Aspirin or heparin or both for improving pregnancy outcomes in women with persistent antiphospholipid antibodies and recurrent pregnancy loss. Cochrane Database Syst Rev. 2020 May 2;5(5):CD012852. doi: 10.1002/14651858.CD012852.pub2.
Results Reference
derived

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

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