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PROSPER: PostpaRtum PrOphylaxiS for PE Randomized Control Trial Pilot (PROSPER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01274637
Recruitment Status : Completed
First Posted : January 11, 2011
Results First Posted : August 1, 2017
Last Update Posted : August 1, 2017
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

Tracking Information
First Submitted Date  ICMJE January 10, 2011
First Posted Date  ICMJE January 11, 2011
Results First Submitted Date  ICMJE January 10, 2017
Results First Posted Date  ICMJE August 1, 2017
Last Update Posted Date August 1, 2017
Study Start Date  ICMJE March 2011
Actual Primary Completion Date January 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 5, 2017)
Feasibility of Recruitment and Trial Operations. [ Time Frame: 4 months ]
The average number of subjects that are recruited per site per month during a 4 month active recruitment phase at each site.
Original Primary Outcome Measures  ICMJE
 (submitted: January 10, 2011)
Feasibility of recruitment and trial operations. [ Time Frame: 6 months ]
The number of subjects that are recruited per site per month during a 6 month active recruitment phase at each site. Secondary measures of feasibility will include:
  • Consent rate for eligible women and reasons for non-consent
  • Rates of compliance with blinded study drug administration
  • Rates of compliance with primary outcome assessment
  • Rates of withdrawal or loss to follow-up within 90 days
  • Length of time required to obtain ethics approval and institutional approvals for conducting the study at Canadian and US sites.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 5, 2017)
  • Venous Thromboembolism in the Early Postpartum Period. [ Time Frame: From randomization to Day 10 ]
    This includes symptomatic Deep Vein Thrombosis (DVT) or pulmonary embolism (PE) in the interval between randomization and the last dose of study drug (10 days +/- 3 days) OR asymptomatic proximal DVT detected by compression ultrasound of both legs done within 24hrs of the last dose of study drug (10 days (+/- 3 days) postpartum). Compressed and non-compressed images will be obtained from the calf trifurcation to the inguinal ligament. All suspected outcomes will be adjudicated by a blinded expert adjudication committee.
  • Late Symptomatic Venous Thromboembolism [ Time Frame: From Day 10 to Day 90 ]
    This includes symptomatic Deep Vein Thrombosis or Pulmonary Embolism. Suspected outcomes will be adjudicated by a blinded adjudication committee.
  • Death From Venous Thromboembolism [ Time Frame: From Randomization to Day 90 ]
    If a subject dies between randomization and late postpartum follow up (Day 90 +/- 7 days) the death will be adjudicated as certain, highly probable, probable, or unlikely due to Pulmonary Embolism (PE) using the following criteria. Certain: hypotension, hypoxia, cardiac arrest with no other explanation other than PE and autopsy or radiographic confirmation Highly probable: criteria for certain but another disease could have caused the death Probable: other cause suspected based on clinical evidence but 100% certainty not available Unlikely: all other cases.
  • Major Bleeding or Clinically Relevant Non-major Bleeding [ Time Frame: From Randomization to Day 90 ]
    Major bleeding meets at least one of the following: Fatal bleeding; Symptomatic bleeding in a critical area or organ (intracranial, intraspinal, retroperitoneal, etc.); Bleeding causing a fall in hemoglobin level of 20 g L-1 (1.24 mmol L-1) or more, or leading to transfusion of two or more units of whole blood or red cells . Clinically Relevant Non-major Bleeding does not meet the criteria for major bleeding but meets at least one of the following: Hospitalization; Medical intervention; Unscheduled contact with a physician; Discomfort (pain, or impairment of activities of daily life).
  • Heparin Induced Thrombocytopenia [ Time Frame: From Randomization to Day 90 ]
    All subjects who develop thrombocytopenia (platelets less than 80 x 109/L and/or with >50% decrease from baseline) will be investigated for Heparin Induced Thrombocytopenia (HIT) by having ELISA and serotonin release assays to confirm or refute a diagnosis of HIT. HIT will be diagnosed with a positive PF4 (platelet factor 4) HIT ELISA assay.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2011)
  • Venous Thromboembolism in the early postpartum period. [ Time Frame: From randomization to Day 21 ]
    This includes symptomatic Deep Vein Thrombosis (DVT) or pulmonary embolism (PE) in the interval between randomization and the last dose of study drug (3 weeks+/- 3 days) OR asymptomatic proximal DVT detected by compression ultrasound of both legs done within 24hrs of the last dose of study drug (3 weeks (+/- 3 days) postpartum). Compressed and non-compressed images will be obtained from the calf trifurcation to the inguinal ligament. All suspected outcomes will be adjudicated by a blinded expert adjudication committee.
  • Late symptomatic Venous Thromboembolism [ Time Frame: From Day 21 to Day 90 ]
    This includes symptomatic Deep Vein Thrombosis or Pulmonary Embolism. Suspected outcomes will be adjudicated by a blinded adjudication committee.
  • Death From Venous Thromboembolism [ Time Frame: From Randomization to Day 90 ]
    If a subject dies between randomization and late postpartum follow up (Day 90 +/- 7 days) the death will be adjudicated as certain, highly probable, probable, or unlikely due to Pulmonary Embolism (PE) using the following criteria. Certain: hypotension, hypoxia, cardiac arrest with no other explanation other than PE and autopsy or radiographic confirmation Highly probable: criteria for certain but another disease could have caused the death Probable: other cause suspected based on clinical evidence but 100% certainty not available Unlikely: all other cases.
  • Major Bleeding or clinically relevant non-major bleeding [ Time Frame: From Randomization to Day 90 ]
    Major bleeding meets at least one of the following: Fatal bleeding; Symptomatic bleeding in a critical area or organ (intracranial, intraspinal, retroperitoneal, etc.); Bleeding causing a fall in hemoglobin level of 20 g L-1 (1.24 mmol L-1) or more, or leading to transfusion of two or more units of whole blood or red cells . Clinically Relevant Non-major Bleeding does not meet the criteria for major bleeding but meets at least one of the following: Hospitalization; Medical intervention; Unscheduled contact with a physician; Discomfort (pain, or impairment of activities of daily life).
  • Heparin Induced Thrombocytopenia [ Time Frame: From Randomization to Day 90 ]
    All subjects who develop thrombocytopenia (platelets less than 80 x 109/L and/or with >50% decrease from baseline) will be investigated for Heparin Induced Thrombocytopenia (HIT) by having ELISA and serotonin release assays to confirm or refute a diagnosis of HIT. HIT will be diagnosed with a positive PF4 HIT ELISA assay.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PROSPER: PostpaRtum PrOphylaxiS for PE Randomized Control Trial Pilot
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Venous Thromboembolism
  • Postpartum
Intervention  ICMJE Drug: Dalteparin Sodium
5,000 IU/0.2ml (anti-Xa) administered once daily in prefilled glass syringes.
Other Names:
  • Fragmin
  • Dalteparin Sodium(DIN 02132648/NDC# 62856-500)
Study Arms  ICMJE
  • Experimental: 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.
    Intervention: Drug: Dalteparin Sodium
  • No Intervention: Control Group
    No treatment control group.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 5, 2017)
62
Original Estimated Enrollment  ICMJE
 (submitted: January 10, 2011)
384
Actual Study Completion Date  ICMJE January 2014
Actual Primary Completion Date January 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01274637
Other Study ID Numbers  ICMJE 2010303-01H
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Ottawa Hospital Research Institute
Original Responsible Party Dr. Marc Rodger, Principal Investigator, Ottawa Hospital Research Institute
Current Study Sponsor  ICMJE Ottawa Hospital Research Institute
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Canadian Institutes of Health Research (CIHR)
Investigators  ICMJE
Principal Investigator: Marc A Rodger, M.D., MSc. Ottawa Hospital Research Institute
PRS Account Ottawa Hospital Research Institute
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP