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

• 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: Ottawa Hospital Research Institute
• Collaborator: Canadian Institutes of Health Research (CIHR)
• Information provided by (Responsible Party): Ottawa Hospital Research Institute

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Conditions: Venous Thromboembolism; Postpartum
• Intervention: Drug: Dalteparin Sodium
• Enrollment: 62

Participant Flow

Recruitment Details	Potential subjects were initially approached by a member of the health care team providing their care (physician, nurse, care facilitator, etc.). If the patient agreed to being contacted, the Investigator or designate provided detailed information regarding the study and assessed the individual's eligibility for the study.
Pre-assignment Details

Arm/Group Title	Low Molecular Weight Heparin	Control Group
Arm/Group Description	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. Dalteparin Sodium: 5,000 IU/0.2ml (anti-Xa) administered once daily in prefilled glass syringes.	No treatment control group.
Period Title: Overall Study
Started	30	32
Completed	30	30
Not Completed	0	2
Reason Not Completed
Withdrawal by Subject	0	1
Lost to Follow-up	0	1

Baseline Characteristics

Arm/Group Title		Low Molecular Weight Heparin	Control Group	Total
Arm/Group Description		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. Dalteparin Sodium: 5,000 IU/0.2ml (anti-Xa) administered once daily in prefilled glass syringes.	No treatment control group.	Total of all reporting groups
Overall Number of Baseline Participants		30	32	62
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	30 participants	32 participants	62 participants
		30.0; (20 to 43)	31.6; (18 to 38)	30.8; (18 to 43)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	32 participants	62 participants
	Female	30 100.0%	32 100.0%	62 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	32 participants	62 participants
	Hispanic or Latino	2 6.7%	2 6.3%	4 6.5%
	Not Hispanic or Latino	28 93.3%	30 93.8%	58 93.5%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	32 participants	62 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	1 3.3%	2 6.3%	3 4.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	4 13.3%	3 9.4%	7 11.3%
	White	24 80.0%	27 84.4%	51 82.3%
	More than one race	1 3.3%	0 0.0%	1 1.6%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	30 participants	32 participants	62 participants
Canada		27	28	55
United States		3	4	7

Outcome Measures

1. Primary Outcome

Title	Feasibility of Recruitment and Trial Operations.
Description	The average number of subjects that are recruited per site per month during a 4 month active recruitment phase at each site.
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Molecular Weight Heparin	Control Group
Arm/Group Description:	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. Dalteparin Sodium: 5,000 IU/0.2ml (anti-Xa) administered once daily in prefilled glass syringes.	No treatment control group.
Overall Number of Participants Analyzed	30	32
Measure Type: Number; Unit of Measure: participants per site per month
	0.9	0.9

2. Secondary Outcome

Title	Venous Thromboembolism in the Early Postpartum Period.
Description	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.
Time Frame	From randomization to Day 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Molecular Weight Heparin	Control Group
Arm/Group Description:	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. Dalteparin Sodium: 5,000 IU/0.2ml (anti-Xa) administered once daily in prefilled glass syringes.	No treatment control group.
Overall Number of Participants Analyzed	30	30
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

3. Secondary Outcome

Title	Late Symptomatic Venous Thromboembolism
Description	This includes symptomatic Deep Vein Thrombosis or Pulmonary Embolism. Suspected outcomes will be adjudicated by a blinded adjudication committee.
Time Frame	From Day 10 to Day 90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Molecular Weight Heparin	Control Group
Arm/Group Description:	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. Dalteparin Sodium: 5,000 IU/0.2ml (anti-Xa) administered once daily in prefilled glass syringes.	No treatment control group.
Overall Number of Participants Analyzed	30	30
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

4. Secondary Outcome

Title	Death From Venous Thromboembolism
Description	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.
Time Frame	From Randomization to Day 90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Molecular Weight Heparin	Control Group
Arm/Group Description:	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. Dalteparin Sodium: 5,000 IU/0.2ml (anti-Xa) administered once daily in prefilled glass syringes.	No treatment control group.
Overall Number of Participants Analyzed	30	32
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

5. Secondary Outcome

Title	Major Bleeding or Clinically Relevant Non-major Bleeding
Description	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).
Time Frame	From Randomization to Day 90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Molecular Weight Heparin	Control Group
Arm/Group Description:	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. Dalteparin Sodium: 5,000 IU/0.2ml (anti-Xa) administered once daily in prefilled glass syringes.	No treatment control group.
Overall Number of Participants Analyzed	30	32
Measure Type: Count of Participants; Unit of Measure: Participants
	3 10.0%	1 3.1%

6. Secondary Outcome

Title	Heparin Induced Thrombocytopenia
Description	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.
Time Frame	From Randomization to Day 90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Molecular Weight Heparin	Control Group
Arm/Group Description:	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. Dalteparin Sodium: 5,000 IU/0.2ml (anti-Xa) administered once daily in prefilled glass syringes.	No treatment control group.
Overall Number of Participants Analyzed	30	32
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Low Molecular Weight Heparin	Control Group
Arm/Group Description	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. Dalteparin Sodium: 5,000 IU/0.2ml (anti-Xa) administered once daily in prefilled glass syringes.	No treatment control group.
All-Cause Mortality
	Low Molecular Weight Heparin	Control Group
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Low Molecular Weight Heparin	Control Group
	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/30 (6.67%)	0/32 (0.00%)
Infections and infestations
Hospitalization † [1]	1/30 (3.33%)	0/32 (0.00%)
Pregnancy, puerperium and perinatal conditions
Hospitalization † [2]	1/30 (3.33%)	0/32 (0.00%)
† Indicates events were collected by systematic assessment; [1] Hospitalization for post-partum infection; [2] Hospitalization for post-partum bleeding event
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Low Molecular Weight Heparin	Control Group
	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/30 (10.00%)	0/32 (0.00%)
Blood and lymphatic system disorders
Abnormal Lab result † [1]	1/30 (3.33%)	0/32 (0.00%)
Infections and infestations
Cellulitis † [2]	1/30 (3.33%)	0/32 (0.00%)
Cellulitis † [3]	1/30 (3.33%)	0/32 (0.00%)
† Indicates events were collected by systematic assessment; [1] Critically low hemoglobin; [2] Cellulitis of c-section incision; [3] Cellulitis of left lower leg, resolving with antibiotics

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Marc Rodger
• Organization: Ottawa Hospital Research Institute
• Phone: 6137388899
• EMail: mrodger@ohri.ca

Publications of Results:

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Ottawa Hospital Research Institute
• ClinicalTrials.gov Identifier: NCT01274637
• Other Study ID Numbers: 2010303-01H
• First Submitted: January 10, 2011
• First Posted: January 11, 2011
• Results First Submitted: January 10, 2017
• Results First Posted: August 1, 2017
• Last Update Posted: August 1, 2017