Postpartum Prophylaxis for PE Randomized Control Trial Pilot: A Pilot Study Assessing Feasibility of a Randomized, Open-label Trial of Low-Molecular-Weight-Heparin for Postpartum Prophylaxis in Women at Risk of Developing Venous Thromboembolism
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 7
- 主要终点
- Feasibility of Recruitment and Trial Operations.
研究概览
简要总结
The purpose of this study is to determine if it is feasible to conduct a multi-center randomized trial to determine whether a blood thinner, low-molecular-weight-heparin (LMWH), is effective at preventing blood clots, thromboembolism (VTE), in postpartum women at risk.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women must be at high risk for thromboembolism for one of the following reasons:
- •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).
- •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:
- •Postpartum infection (fever (temperature>38.5oC) and clinical signs/symptoms of infection and elevated neutrophil count (higher than local lab normal))
- •Postpartum hemorrhage (Estimated blood loss >1000 ml during delivery and postpartum)
- •Pre-pregnancy BMI >25 kg/m2
- •Emergency cesarean birth (emergency = not planned prior to onset of labour)
- •Smoking >5 cigarettes per day prior to pregnancy
- •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.
- •Infant birth weight (adjusted for sex and gestational age) <3rd percentile (i.e., small for gestational age).
排除标准
- •Less than 6 hours or more than 36 hours since delivery at the time of randomization
- •Need for anticoagulation as judged by the local investigator, may include but not limited to:
- •Personal history of previous provoked or unprovoked VTE (DVT or PE)
- •Continuation of LMWH that was started in the antenatal period for VTE prophylaxis
- •Mechanical heart valve
- •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).
- •Contraindication to heparin therapy, including:
- •History of heparin induced thrombocytopenia (HIT)
- •Platelet count of less than 80,000 x 106/L on postpartum Complete Blood Count(CBC)
- •Hemoglobin ≤ 75 g/L on postpartum CBC
- •Active bleeding at any site (not resolved prior to randomization)
- •Excessive postpartum vaginal bleeding (>1 pad per hour prior to randomization).
- •Documented gastrointestinal ulcer within 6 weeks prior to randomization
- •History of heparin or LMWH allergy
- •Severe postpartum hypertension (systolic blood pressure (SBP) > 200mm/hg and/or diastolic blood pressure (DBP) > 120mm/hg)
- •Severe hepatic failure (INR >1.8 if liver disease suspected)
- •Have received more than one dose of heparin or LMWH since delivery
- •< age of legal majority in local jurisdiction (age <18 in Canada)
- •Prior participation in PROSPER
- •Unable or refused to consent
研究组 & 干预措施
low molecular weight heparin
Prophylactic-dose (5000 IU/0.2ml)low molecular weight heparin (LMWH), administered subcutaneously once daily in pre-filled glass syringes for 10 days (+/- 3 days) for a total of 10 (+/-3) study drug injections.
干预措施: Dalteparin Sodium (Drug)
结局指标
主要结局
Feasibility of Recruitment and Trial Operations.
时间窗: 4 months
The average number of subjects that are recruited per site per month during a 4 month active recruitment phase at each site.
次要结局
- Venous Thromboembolism in the Early Postpartum Period.(From randomization to Day 10)
- Late Symptomatic Venous Thromboembolism(From Day 10 to Day 90)
- Heparin Induced Thrombocytopenia(From Randomization to Day 90)
- Death From Venous Thromboembolism(From Randomization to Day 90)
- Major Bleeding or Clinically Relevant Non-major Bleeding(From Randomization to Day 90)