PROSPER: PostpaRtum PrOphylaxiS for PE Randomized Control Trial Pilot

The PROPSER pilot is a randomized, open-label pilot study comparing prophylactic low
molecular weight heparin (LMWH) to saline placebo. The PROSPER pilot study will assess the
feasibility of conducting a full trial as measured by the number of subjects recruited per
center per month. In addition, clinical data will be collected to determine an estimate of
the primary outcome event rate (symptomatic VTE or asymptomatic proximal deep vein
thrombosis (DVT) and major bleeding event rate for the full trial in LMWH and control
groups. If our pilot results indicate that no substantial changes are needed to the study
design, we will include the pilot data in the primary and secondary outcome analyses for the
full trial (i.e. a "Vanguard trial" or internal pilot trial).

Eligible consenting women at risk of postpartum thrombosis will be randomized within 36
hours after delivery of the placenta and will be equally allocated to 2 trial arms, either
the treatment group: prophylactic-dose LMWH, subcutaneously once daily for 10 days (+/-3
days), or the control group.

At 10 days (+/- 3 days), all women will have a study visit to assess for study outcomes,
including bilateral leg ultrasound screening for VTE and a D-dimer test. A final telephone
follow-up will occur at 90 days for outcome assessment of subsequent VTE, bleeding or other
adverse events.

Inclusion Criteria:

Women must be at high risk for thromboembolism for one of the following reasons:

1. Known low risk thrombophilia (Known = diagnosed prior to enrollment and low risk
thrombophilia includes heterozygous factor V Leiden or prothrombin gene variant or
protein C deficiency or protein S deficiency. If not previously tested then assumed
not to have thrombophilia).

2. Immobilization (defined as >90% of waking hours in bed, of a week or more at any
point in the antepartum period).

OR any two of the following reasons:

1. Postpartum infection (fever (temperature>38.5oC) and clinical signs/symptoms of
infection and elevated neutrophil count (higher than local lab normal))

2. Postpartum hemorrhage (Estimated blood loss >1000 ml during delivery and postpartum)

3. Pre-pregnancy BMI >25 kg/m2

4. Emergency cesarean birth (emergency = not planned prior to onset of labour)

5. Smoking >5 cigarettes per day prior to pregnancy

6. Preeclampsia (blood pressure ≥ 140mmHG systolic and/or ≥90 mmHg diastolic on at least
one occasion and proteinuria (1+ on urine dipstick or 300mg/dl or total excretion of
300mg/24 hours) or typical end-organ dysfunction.

7. Infant birth weight (adjusted for sex and gestational age) <3rd percentile (i.e.,
small for gestational age).

Exclusion Criteria:

1. Less than 6 hours or more than 36 hours since delivery at the time of randomization

2. Need for anticoagulation as judged by the local investigator, may include but not
limited to:

1. Personal history of previous provoked or unprovoked VTE (DVT or PE)

2. Continuation of LMWH that was started in the antenatal period for VTE
prophylaxis

3. Mechanical heart valve

4. Known high-risk thrombophilia (Known = diagnosed prior to enrolment and
high-risk thrombophilia includes deficiency of antithrombin (at least 1 abnormal
lab result), persistently positive anticardiolipin antibodies (> 30U/ml on two
measurements a minimum of six weeks apart), persistently positive Anti B2
glycoprotein antibodies (> 20U/ml on two measurements a minimum of six weeks
apart), persistently positive lupus anticoagulant (positive on two measurements
a minimum of six weeks apart), homozygous factor V Leiden (FVL), homozygous
prothrombin gene mutation (PGM), compound heterozygosity factor V Leiden (FVL)
and prothrombin gene mutations (PGM), more than 1 thrombophilia (any combination
of 2 or more: FVL, PGM, protein C deficiency, protein S deficiency). If not
previously tested then assumed not to have thrombophilia).

3. Contraindication to heparin therapy, including:

1. History of heparin induced thrombocytopenia (HIT)

2. Platelet count of less than 80,000 x 106/L on postpartum Complete Blood
Count(CBC)

3. Hemoglobin ≤ 75 g/L on postpartum CBC

4. Active bleeding at any site (not resolved prior to randomization)

5. Excessive postpartum vaginal bleeding (>1 pad per hour prior to randomization).

6. Documented gastrointestinal ulcer within 6 weeks prior to randomization

7. History of heparin or LMWH allergy

8. Severe postpartum hypertension (systolic blood pressure (SBP) > 200mm/hg and/or
diastolic blood pressure (DBP) > 120mm/hg)

9. Severe hepatic failure (INR >1.8 if liver disease suspected)

4. Have received more than one dose of heparin or LMWH since delivery

5. < age of legal majority in local jurisdiction (age <18 in Canada)

6. Prior participation in PROSPER

7. Unable or refused to consent