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

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ClinicalTrials.gov Identifier: NCT03100123
Recruitment Status : Terminated (Pilot deemed not feasible by Steering Committee due to recruitment rate.)
First Posted : April 4, 2017
Results First Posted : April 8, 2020
Last Update Posted : April 8, 2020
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Antiphospholipid Syndrome in Pregnancy Pregnancy Loss Drug: Aspirin 81 mg Drug: Low-molecular-weight heparin Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
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
Actual Study Start Date : November 6, 2017
Actual Primary Completion Date : October 7, 2019
Actual Study Completion Date : October 7, 2019

Arm Intervention/treatment
Active Comparator: Standard of Care Arm
Open-label low-molecular-weight heparin (LMWH) prophylaxis until 37 weeks gestation AND low-dose aspirin daily until delivery.
Drug: Low-molecular-weight heparin
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.
Other Names:
  • Tinzaparin
  • Dalteparin
  • Enoxaparin
  • LMWH

Experimental: Experimental Arm
Open-label low-dose Aspirin 81 mg daily from randomization until delivery.
Drug: Aspirin 81 mg
Aspirin 81 mg po daily in tablet form.
Other Name: Acetylsalicylic Acid

Primary Outcome Measures :
  1. Study Feasibility: Mean Recruitment Rate Per Center Per Month [ Time Frame: 24 months ]
    The primary feasibility outcome of the pilot trial is the mean recruitment rate per center per month.

Secondary Outcome Measures :
  1. Essential Documents [ Time Frame: 18 months ]
    Proportion of sites requiring >18 months to obtain all required approvals/contracts from time of delivery of all study documents.

  2. Eligibility [ Time Frame: 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).

  3. Consent [ Time Frame: 24 months ]
    Proportion of eligible subjects who provide consent.

  4. Withdrawals/Loss to Follow-up [ Time Frame: 24 months ]
    Proportion of withdrawals/loss to follow-up among randomized patients.

  5. Crossover Rate [ Time Frame: 52 weeks ]
    Crossover rate between standard of care and experimental study arms.

  6. Study Drug Compliance [ Time Frame: 52 weeks ]
    Level of compliance with study drug through patient recall and patient medication diary.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03100123

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Canada, Ontario
Ottawa Hospital Research Institute
Ottawa, Ontario, Canada
Sponsors and Collaborators
Ottawa Hospital Research Institute
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Principal Investigator: Marc Rodger, MD Ottawa Hospital Research Institute
Principal Investigator: Leslie Skeith, MD Ottawa Hospital Research Institute
  Study Documents (Full-Text)

Documents provided by Ottawa Hospital Research Institute:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT03100123    
Other Study ID Numbers: CTO 0807
First Posted: April 4, 2017    Key Record Dates
Results First Posted: April 8, 2020
Last Update Posted: April 8, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Abortion, Spontaneous
Fetal Death
Antiphospholipid Syndrome
Pathologic Processes
Pregnancy Complications
Autoimmune Diseases
Immune System Diseases
Heparin, Low-Molecular-Weight
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors