Venous ThromboembolismPhase 3PROSPERNCT01274637
PROSPER: PostpaRtum PrOphylaxiS for PE Randomized Control Trial Pilot
A Phase 3 study testing Dalteparin Sodium in people with Venous Thromboembolism and Postpartum, run by Ottawa Hospital Research Institute at 7 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Venous Thromboembolism, Postpartum
- What is being tested?
- Dalteparin Sodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Mar 2011to Jan 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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).
Who cannot join
- 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).
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- 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
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
Canada5 sites
Royal Alexandra Hospital
Edmonton, Alberta
McMaster University Medical Centre
Hamilton, Ontario, L8N 3Z5
SMBD Jewish General Hospital
Montreal, Quebec
Ottawa Hospital General Campus & Civic Campus
Ottawa, Ontario, K1H 8L6
Sunnybrook Health Sciences Centre
Toronto, Ontario
United States2 sites
University of Virginia Medical Center
Charlottesville, Virginia, 22908
Puget Sound Blood Center
Seattle, Washington, 98104
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Venous Thromboembolism, Postpartum
- Being tested
- Dalteparin Sodium
- Keywords
- postpartum, low molecular weight heparin, venous thromboembolism, prophylaxis, Dalteparin Sodium
- Medical subject headings
- Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dalteparin SodiumDrug
Also called Fragmin, Dalteparin Sodium(DIN 02132648/NDC# 62856-500)
5,000 IU/0.2ml (anti-Xa) administered once daily in prefilled glass syringes.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Dalteparin Sodium |
| Control Group | No intervention | No treatment control group. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 months
Secondary outcomes (5)
Venous Thromboembolism in the Early Postpartum Period.
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.
Measured: From randomization to Day 10
Late Symptomatic Venous Thromboembolism
This includes symptomatic Deep Vein Thrombosis or Pulmonary Embolism. Suspected outcomes will be adjudicated by a blinded adjudication committee.
Measured: From Day 10 to Day 90
Death From Venous Thromboembolism
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.
Measured: From Randomization to Day 90
Major Bleeding or Clinically Relevant Non-major Bleeding
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).
Measured: From Randomization to Day 90
Heparin Induced Thrombocytopenia
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.
Measured: From Randomization to Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2011 (estimated)
- Study startMar 2011
- Primary completionJan 2014
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Marc A Rodger, M.D., MSc., Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01274637
- Sponsor's protocol ID
- 2010303-01H
- Acronym
- PROSPER
- Status last verified
- Jan 2017
- First submitted
- 10 Jan 2011
- Last updated
- 1 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 27096813Rodger 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.
PubMed 25373438Middleton 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.
PubMed 33779986
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01274637
- Acronym / sponsor ID
- PROSPER / 2010303-01H
- Conditions
- Venous Thromboembolism, Postpartum
- Keywords
- postpartum, low molecular weight heparin, venous thromboembolism, prophylaxis, Dalteparin Sodium
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- Mar 2011
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 11 Jan 2011 (estimated)
- Results
- Posted 1 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| low molecular weight heparin | Experimental | Drug: Dalteparin SodiumProphylactic-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. |
| Control Group | No intervention | –No treatment control group. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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).
- 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
Key exclusion criteria (20 listed)
- 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:
- Contraindication to heparin therapy, including:
- Have received more than one dose of heparin or LMWH since delivery
- < age of legal majority in local jurisdiction (age <18 in Canada)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dalteparin SodiumAlso: Fragmin, Dalteparin Sodium(DIN 02132648/NDC# 62856-500)5,000 IU/0.2ml (anti-Xa) administered once daily in prefilled glass syringes. | Drug | low molecular weight heparin |
Primary outcome
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.
5 secondary outcomes
Venous Thromboembolism in the Early Postpartum Period.
Time frame: From randomization to Day 10
Late Symptomatic Venous Thromboembolism
Time frame: From Day 10 to Day 90
Death From Venous Thromboembolism
Time frame: From Randomization to Day 90
Major Bleeding or Clinically Relevant Non-major Bleeding
Time frame: From Randomization to Day 90
Heparin Induced Thrombocytopenia
Time frame: From Randomization to Day 90
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27096813Rodger 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.
- Results publication: PubMed 25373438Rodger 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.
- Derived from this study: PubMed 33779986Middleton 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc A Rodger, M.D., MSc. principal investigator
Ottawa Hospital Research Institute
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dalteparin Sodium in people with Venous Thromboembolism and Postpartum, run by Ottawa Hospital Research Institute at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of Recruitment and Trial Operations. (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01274637, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2017.