PREVENTIHS: PREvention of VENous Thromboembolism In Hemorrhagic Stroke Patients

• Sponsor: University Of Perugia (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01573169
• Collaborator: (none)
• Enrollment: 73
• Location: 1
• Arms: 2
• Duration (Months): 94
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

Patients with cerebral hemorrhage (ICH) have a high risk of venous thromboembolism. Intermittent pneumatic compression combined with elastic stockings have been shown to be superior to elastic stockings alone in reducing the rate of asymptomatic deep vein thrombosis after ICH in a randomized trial (4.7% vs. 15.9%). Graduated compression stockings alone are ineffective in preventing deep vein thrombosis in patients with ischemic or hemorrhagic stroke. Less clear is the role of anticoagulation in the prevention of venous thromboembolism in patients with ICH because the use of anticoagulants may cause an enlargement of the hematoma. In a multicenter, randomized trial, the investigators will assess the efficacy and safety of enoxaparin in the prevention of venous thromboembolism in patients with spontaneous intracerebral hemorrhage. Enoxaparin (40 mg once daily) or standard therapy (graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization) will be given subcutaneously for not less than 10 days beginning after 72 hours from stroke onset.

Condition or Disease	Intervention/Treatment	Phase
Hemorrhagic Stroke; Venous Thromboembolism; Deep Venous Thrombosis	Drug: Enoxaparin; Other: Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: PREvention of VENous Thromboembolism In Hemorrhagic Stroke Patients
• Study Start Date: May 1, 2012
• Actual Primary Completion Date: Mar 1, 2020
• Actual Study Completion Date: Mar 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: low weight molecular heparin enoxaparin 0.4 ml subcutaneous per day	Drug: Enoxaparin; enoxaparin 0.4 ml sc per day for 10 days started 72 hours after the stroke
Placebo Comparator: standard therapy Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization	Other: Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization; placebo standard therapy

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Symptomatic and Asymptomatic Venous Thromboembolism [10 days]

   Symptomatic venous thromboembolism (deep venous thrombosis and/or pulmonary embolism) and asymptomatic deep venous thrombosis on ultrasound examination

Secondary Outcome Measures

1. Bleedings [90 days]

   symptomatic and asymptomatic intra and extracranial bleedings

2. Mortality [90 days]

   mortality of any cause

3. Disability [90 days]

   modified Rankin Scale (mRS) equal to and greater than 3. 0 - No symptoms. - No significant disability. Able to carry out all usual activities, despite some symptoms. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. - Moderate disability. Requires some help, but able to walk unassisted. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. - Dead.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Intracranial spontaneous hemorrhage on brain CT scan

• Intracranial hemorrhage during treatment with oral anticoagulants

• Bedridden patients (item 6 of NIHSS: motor leg points 3 or 4 or severe ataxia for cerebellar hemorrhage).

Exclusion Criteria:

• cerebral hemorrhage due to intracranial vascular malformation

• rebleeding on CT scan after 72 hours from stroke (before randomization)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stroke Unit	Perugia		Italy	06126

Sponsors and Collaborators

• University Of Perugia

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Jun 1, 2011

More Information

Publications

• Paciaroni M, Agnelli G, Venti M, Alberti A, Acciarresi M, Caso V. Efficacy and safety of anticoagulants in the prevention of venous thromboembolism in patients with acute cerebral hemorrhage: a meta-analysis of controlled studies. J Thromb Haemost. 2011 May;9(5):893-8. doi: 10.1111/j.1538-7836.2011.04241.x.

• Responsible Party: Maurizio Paciaroni, Principal Investigator, University Of Perugia
• ClinicalTrials.gov Identifier: NCT01573169
• Other Study ID Numbers: PREVENTIHS
• First Posted: Apr 6, 2012
• Last Update Posted: Sep 10, 2021
• Last Verified: Sep 1, 2021

• Keywords provided by Maurizio Paciaroni, Principal Investigator, University Of Perugia: hemorrhagic stroke; venous thromboembolism; prevention
• Additional relevant MeSH terms: Stroke; Hemorrhagic Stroke; Thrombosis; Thromboembolism; Venous Thromboembolism; Venous Thrombosis; Enoxaparin

Study Results

Participant Flow

Pre-assignment Detail	No wash-out, nor run-in events.

Arm/Group Title	Low Weight Molecular Heparin	Standard Therapy
Arm/Group Description	enoxaparin 0.4 ml subcutaneous per day Enoxaparin: enoxaparin 0.4 ml sc per day for 10 days started 72 hours after the stroke	Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization: placebo standard therapy
Period Title: Overall Study
STARTED	38	35
COMPLETED	38	35
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Low Weight Molecular Heparin	Standard Therapy	Total
Arm/Group Description	enoxaparin 0.4 ml subcutaneous per day Enoxaparin: enoxaparin 0.4 ml sc per day for 10 days started 72 hours after the stroke	Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization: placebo standard therapy	Total of all reporting groups
Overall Participants	38	35	73
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.4 (13.7)	71.5 (11.6)	70.9 (12.6)
Sex: Female, Male (Count of Participants)
Female	16 42.1%	17 48.6%	33 45.2%
Male	22 57.9%	18 51.4%	40 54.8%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Obesity (Count of Participants)
Count of Participants [Participants]	3 7.9%	3 8.6%	6 8.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Symptomatic and Asymptomatic Venous Thromboembolism
Description	Symptomatic venous thromboembolism (deep venous thrombosis and/or pulmonary embolism) and asymptomatic deep venous thrombosis on ultrasound examination
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Weight Molecular Heparin	Standard Therapy
Arm/Group Description	enoxaparin 0.4 ml subcutaneous per day Enoxaparin: enoxaparin 0.4 ml sc per day for 10 days started 72 hours after the stroke	Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization: placebo standard therapy
Measure Participants	38	35
Count of Participants [Participants]	6 15.8%	7 20%

2. Secondary Outcome

Title	Bleedings
Description	symptomatic and asymptomatic intra and extracranial bleedings
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Weight Molecular Heparin	Standard Therapy
Arm/Group Description	enoxaparin 0.4 ml subcutaneous per day Enoxaparin: enoxaparin 0.4 ml sc per day for 10 days started 72 hours after the stroke	Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization: placebo standard therapy
Measure Participants	38	35
Count of Participants [Participants]	1 2.6%	3 8.6%

3. Secondary Outcome

Title	Mortality
Description	mortality of any cause
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Weight Molecular Heparin	Standard Therapy
Arm/Group Description	enoxaparin 0.4 ml subcutaneous per day Enoxaparin: enoxaparin 0.4 ml sc per day for 10 days started 72 hours after the stroke	Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization: placebo standard therapy
Measure Participants	38	35
Count of Participants [Participants]	7 18.4%	6 17.1%

4. Secondary Outcome

Title	Disability
Description	modified Rankin Scale (mRS) equal to and greater than 3. 0 - No symptoms. - No significant disability. Able to carry out all usual activities, despite some symptoms. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. - Moderate disability. Requires some help, but able to walk unassisted. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. - Dead.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Weight Molecular Heparin	Standard Therapy
Arm/Group Description	enoxaparin 0.4 ml subcutaneous per day Enoxaparin: enoxaparin 0.4 ml sc per day for 10 days started 72 hours after the stroke	Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization: placebo standard therapy
Measure Participants	38	35
Count of Participants [Participants]	27 71.1%	30 85.7%

Adverse Events

Time Frame	3 months
Arm/Group Title	Low Weight Molecular Heparin		Standard Therapy
Arm/Group Description	enoxaparin 0.4 ml subcutaneous per day Enoxaparin: enoxaparin 0.4 ml sc per day for 10 days started 72 hours after the stroke		Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization Graduated compression stockings and/or intermittent pneumatic compression and/or early mobilization: placebo standard therapy
All Cause Mortality
	Low Weight Molecular Heparin		Standard Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/38 (18.4%)		6/35 (17.1%)
Serious Adverse Events
	Low Weight Molecular Heparin		Standard Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/38 (2.6%)		3/35 (8.6%)
Nervous system disorders
Intracranial bleedings	0/38 (0%)	0	3/35 (8.6%)	3
Respiratory, thoracic and mediastinal disorders
extracranial bleeding	1/38 (2.6%)	1	0/35 (0%)	0
Other (Not Including Serious) Adverse Events
	Low Weight Molecular Heparin		Standard Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/35 (0%)

Limitations/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.