PROSPER: PostpaRtum PrOphylaxiS for PE Randomized Control Trial Pilot

NCT01274637 | Completed Phase 3 Results DMC

• 1 other identifier: 2010303-01H
• Study Type: interventional
• Target: 62
• Locations: 2 countries
• Sites: 7

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.

Conditions

Venous Thromboembolism; Postpartum

Keywords

postpartum; low molecular weight heparin; venous thromboembolism; prophylaxis; Dalteparin Sodium

Outcome Measures

Primary Outcomes (1)

• Feasibility of Recruitment and Trial Operations.

  The average number of subjects that are recruited per site per month during a 4 month active recruitment phase at each site.

  4 months

Secondary Outcomes (5)

• Venous Thromboembolism in the Early Postpartum Period.

  From randomization to Day 10

• Late Symptomatic Venous Thromboembolism

  From Day 10 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

• Heparin Induced Thrombocytopenia

  From Randomization to Day 90

Study Arms (2)

low molecular weight heparin

EXPERIMENTAL

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.

Drug: Dalteparin Sodium

Control Group

NO INTERVENTION

No treatment control group.

Interventions

Dalteparin Sodium DRUG

5,000 IU/0.2ml (anti-Xa) administered once daily in prefilled glass syringes.

Also known as: Fragmin, Dalteparin Sodium(DIN 02132648/NDC# 62856-500)

low molecular weight heparin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (7)

University of Virginia Medical Center

Charlottesville, Virginia, 22908, United States

Location

Puget Sound Blood Center

Seattle, Washington, 98104, United States

Location

Royal Alexandra Hospital

Edmonton, Alberta, Canada

Location

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

Ottawa Hospital General Campus & Civic Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

SMBD Jewish General Hospital

Montreal, Quebec, Canada

Location

Related Publications (3)

• Rodger MA, Phillips P, Kahn SR, Bates S, McDonald S, Khurana R, James AH, Konkle BA; PROSPER Investigators: Tim Ramsay, Dean Fergusson, Anne McLeod, Wee Shian Chan, Rshmi Khurana, Kara Narenberg, Haim Abenhaim, John Heit, Ghada Bourjeilly, Paul Gibson, Kent Bailey. Low molecular weight heparin to prevent postpartum venous thromboembolism: A pilot study to assess the feasibility of a randomized, open-label trial. Thromb Res. 2016 Jun;142:17-20. doi: 10.1016/j.thromres.2016.04.004. Epub 2016 Apr 9. No abstract available.

  PMID: 27096813 RESULT

• Rodger MA, Phillips P, Kahn SR, James AH, Konkle BA; PROSPER Investigators. Low-molecular-weight heparin to prevent postpartum venous thromboembolism. A pilot randomised placebo-controlled trial. Thromb Haemost. 2015 Jan;113(1):212-6. doi: 10.1160/TH14-06-0485. Epub 2014 Nov 6.

  PMID: 25373438 RESULT

• Middleton P, Shepherd E, Gomersall JC. Venous thromboembolism prophylaxis for women at risk during pregnancy and the early postnatal period. Cochrane Database Syst Rev. 2021 Mar 29;3(3):CD001689. doi: 10.1002/14651858.CD001689.pub4.

  PMID: 33779986 DERIVED

MeSH Terms

Conditions

Venous Thromboembolism

Interventions

Dalteparin

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Dr. Marc Rodger
• Organization: Ottawa Hospital Research Institute

mrodger@ohri.ca

6137388899

Study Officials

• Marc A Rodger, M.D., MSc.

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2011
• First Posted: January 11, 2011
• Study Start: March 1, 2011
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: August 1, 2017
• Results First Posted: August 1, 2017

Record last verified: 2017-01

Locations

US (2); CA (5)