Antiphospholipid Syndrome in PregnancyEarly Phase 1APPLENCT03100123

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

A Early Phase 1 study testing Aspirin 81 mg and Low-molecular-weight heparin in people with Antiphospholipid Syndrome in Pregnancy and Pregnancy Loss, run by Ottawa Hospital Research Institute at 1 site in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Antiphospholipid Syndrome in Pregnancy, Pregnancy Loss
What is being tested?: Aspirin 81 mg and Low-molecular-weight heparin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1 participants
Where: 1 siteCanada
Study dates: 6 Nov 2017to 7 Oct 2019
Phase: Early Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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;

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

Canada1 site

Ottawa Hospital Research Institute
Ottawa, Ontario

Other trials in Canada

About this study

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

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.

Read the 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.

Conditions: Antiphospholipid Syndrome in Pregnancy, Pregnancy Loss
Being tested: Aspirin 81 mg, Low-molecular-weight heparin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Aspirin 81 mgDrug
Also called Acetylsalicylic Acid
Aspirin 81 mg po daily in tablet form.
Low-molecular-weight heparinDrug
Also called Tinzaparin, Dalteparin, Enoxaparin, LMWH
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.

Study groups in NCT03100123
Study group	Role	What they receive
Standard of Care Arm	Active comparator	Open-label low-molecular-weight heparin (LMWH) prophylaxis until 37 weeks gestation AND low-dose aspirin daily until delivery. Receives: Drug: Low-molecular-weight heparin
Experimental Arm	Experimental	Open-label low-dose Aspirin 81 mg daily from randomization until delivery. Receives: Drug: Aspirin 81 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 24 months

Secondary outcomes (6)

Essential Documents
Proportion of sites requiring >18 months to obtain all required approvals/contracts from time of delivery of all study documents.
Measured: 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).
Measured: 24 months
Consent
Proportion of eligible subjects who provide consent.
Measured: 24 months
Withdrawals/Loss to Follow-up
Proportion of withdrawals/loss to follow-up among randomized patients.
Measured: 24 months
Crossover Rate
Crossover rate between standard of care and experimental study arms.
Measured: 52 weeks
Study Drug Compliance
Level of compliance with study drug through patient recall and patient medication diary.
Measured: 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Nov 20177 Oct 2019

First posted4 Apr 2017
Study start6 Nov 2017
Primary completion7 Oct 2019
Study completion7 Oct 2019

Why it stopped: Pilot deemed not feasible by Steering Committee due to recruitment rate.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Antiphospholipid Syndrome in PregnancyStudies of the same condition, open and under way.
More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Early Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
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)
Enrolment: 1 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03100123
Sponsor's protocol ID: CTO 0807
Acronym: APPLE
Status last verified: Mar 2020
First submitted: 21 Feb 2017
Last updated: 8 Apr 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 32358837

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingObservational study
MENA/Levant Epidemiological, Registry of Immunological & Clinical Traits (MERIT)
Antiphospholipid (aPL)-Positive, Rheumatic Arthritis
RecruitingPhase 1
A Clinical Study of YTS109 Cells for the Treatment of R/R Autoimmune Diseases
Systemic Lupus Erythematosus (SLE), Lupus Nephritis (LN)
RecruitingPhase 1
A Clinical Study of YTS109 Cell for R/R Autoimmune Diseases
Systemic Lupus Erythematosus (SLE), Lupus Nephritis (LN)
RecruitingObservational study
Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS)
Systemic Lupus Erythematosus, Antiphospholipid Syndrome
RecruitingPhase 2
IMPACT Study: IMProve Pregnancy in APS With Certolizumab Therapy
High Risk Pregnancy, Pregnancy Complications

All Antiphospholipid Syndrome in Pregnancy trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03100123
Acronym / sponsor ID: APPLE / CTO 0807
Conditions: Antiphospholipid Syndrome in Pregnancy, Pregnancy Loss
Phase: Early Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Pilot deemed not feasible by Steering Committee due to recruitment rate.
Enrolment: 1 participants (actual)
Lead sponsor: Ottawa Hospital Research InstituteUniversity, hospital or other
Study start: 6 Nov 2017 (actual)
Primary completion: 7 Oct 2019 (actual)
Study completion: 7 Oct 2019 (actual)
First posted: 4 Apr 2017 (actual)
Results: Posted 8 Apr 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
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).

Arm	Type	Receives
Standard of Care Arm	Active comparator	Drug: Low-molecular-weight heparinOpen-label low-molecular-weight heparin (LMWH) prophylaxis until 37 weeks gestation AND low-dose aspirin daily until delivery.
Experimental Arm	Experimental	Drug: Aspirin 81 mgOpen-label low-dose Aspirin 81 mg daily from randomization until delivery.

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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;

Key exclusion criteria (7 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Aspirin 81 mgAlso: Acetylsalicylic AcidAspirin 81 mg po daily in tablet form.	Drug	Experimental Arm
Low-molecular-weight heparinAlso: Tinzaparin, Dalteparin, Enoxaparin, LMWHThe 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.	Drug	Standard of Care Arm

Primary outcome

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.

6 secondary outcomes

Essential Documents
Time frame: 18 months
Eligibility
Time frame: 24 months
Consent
Time frame: 24 months
Withdrawals/Loss to Follow-up
Time frame: 24 months
Crossover Rate
Time frame: 52 weeks
Study Drug Compliance
Time frame: 52 weeks

Results and safety

Results posted to the registry on 8 Apr 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Standard of Care Arm	0	0
Experimental Arm	1	1

Primary outcome: Study Feasibility: Mean Recruitment Rate Per Center Per Month

Time frame: 24 months. Number. Unit: participants

Measure	Standard of Care Arm n = 0	Experimental Arm n = 1
Value	–	1

Population analysed: 1 participant was recruited (ASA alone arm) and the pilot trial was stopped early due to feasibility.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: The AE reporting period for this trial begun upon randomization, and ended 30 days after receiving the last dose of study drug.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Standard of Care Arm	0 of 0	0 of 0	0
Experimental Arm	0 of 1 (0%)	0 of 1 (0%)	0 of 1

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32358837Hamulyak 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.
Individual participant dataSharing planned: No

Related trials for Antiphospholipid Syndrome in Pregnancy

Not yet recruitingObservational study
MENA/Levant Epidemiological, Registry of Immunological & Clinical Traits (MERIT)
Antiphospholipid (aPL)-Positive, Rheumatic Arthritis
RecruitingPhase 1
A Clinical Study of YTS109 Cells for the Treatment of R/R Autoimmune Diseases
Systemic Lupus Erythematosus (SLE), Lupus Nephritis (LN)
RecruitingPhase 1
A Clinical Study of YTS109 Cell for R/R Autoimmune Diseases
Systemic Lupus Erythematosus (SLE), Lupus Nephritis (LN)
RecruitingObservational study
Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS)
Systemic Lupus Erythematosus, Antiphospholipid Syndrome
RecruitingPhase 2
IMPACT Study: IMProve Pregnancy in APS With Certolizumab Therapy
High Risk Pregnancy, Pregnancy Complications

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Marc Rodger, MD principal investigator

Ottawa Hospital Research Institute

Leslie Skeith, MD principal investigator

Ottawa Hospital Research Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Study Feasibility: Mean Recruitment Rate Per Center Per Month (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03100123, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2020.