Antiphospholipid Syndrome in Pregnancy, Pregnancy Loss
Conditions
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.
Interventions
DRUGAspirin 81 mg
Aspirin 81 mg po daily in tablet form.
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.
Sponsors
Ottawa Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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).
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Essential Documents | 18 months | Proportion of sites requiring \>18 months to obtain all required approvals/contracts from time of delivery of all study documents. |
| Crossover Rate | 52 weeks | Crossover rate between standard of care and experimental study arms. |
| Study Drug Compliance | 52 weeks | Level of compliance with study drug through patient recall and patient medication diary. |
| Withdrawals/Loss to Follow-up | 24 months | Proportion of withdrawals/loss to follow-up among randomized patients. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care Arm Open-label low-molecular-weight heparin (LMWH) prophylaxis until 37 weeks gestation AND low-dose aspirin daily until delivery.
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. | 0 |
| Experimental Arm Open-label low-dose Aspirin 81 mg daily from randomization until delivery.
Aspirin 81 mg: Aspirin 81 mg po daily in tablet form. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Standard of Care Arm | Experimental Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Canada | — | 1 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 1 |
| other Total, other adverse events | 0 / 0 | 0 / 1 |
| serious Total, serious adverse events | 0 / 0 | 0 / 1 |
Outcome results
Primary
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.
Time frame: 24 months
Population: 1 participant was recruited (ASA alone arm) and the pilot trial was stopped early due to feasibility.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental Arm | Study Feasibility: Mean Recruitment Rate Per Center Per Month | 1 participants |
Secondary
Consent
Proportion of eligible subjects who provide consent.
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care Arm | Consent | 1 Participants |
Secondary
Crossover Rate
Crossover rate between standard of care and experimental study arms.
Time frame: 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care Arm | Crossover Rate | 0 Participants |
Secondary
Eligibility
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care Arm | Eligibility | 4 Participants |
Secondary
Essential Documents
Proportion of sites requiring \>18 months to obtain all required approvals/contracts from time of delivery of all study documents.
Time frame: 18 months
Population: Site #1 was able to obtain all applicable approvals and begin recruitment in 12 months. Not applicable applicable for site #2 as study was closed early due to low recruitment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care Arm | Essential Documents | 1 Sites |
Secondary
Study Drug Compliance
Level of compliance with study drug through patient recall and patient medication diary.
Time frame: 52 weeks
Population: No participants in standard of care arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care Arm | Study Drug Compliance | 0 Participants |
| Experimental Arm | Study Drug Compliance | 1 Participants |
Secondary
Withdrawals/Loss to Follow-up
Proportion of withdrawals/loss to follow-up among randomized patients.
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care Arm | Withdrawals/Loss to Follow-up | 0 Participants |