Using Intravenous Heparin Versus Standard of Care Subcutaneous Heparin to Prevent Clots After Surgery

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT01608906
• Collaborator: (none)
• Enrollment: 152
• Location: 1
• Arms: 2
• Duration (Months): 84
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

This study plans to learn more about what is the best treatment to prevent blood clots in patients in intensive care units (ICU's). The investigators know that patients who are in ICU's have a higher than normal risk of getting blood clots in the veins of their arms or legs. This can be very dangerous as the clot may move into the lungs. To prevent this, the standard treatment is to give low dose heparin subcutaneously 3 times a day (usually 5000 units at each dose). In this study the investigators are randomizing patients to receive either standard of care or low dose intravenous heparin in a continuous infusion.

Condition or Disease	Intervention/Treatment	Phase
Venous Thrombosis	Drug: low dose intravenous heparin (LDIVH); Drug: Heparin	N/A

Detailed Description

Macro- and micro-thrombosis both contribute significantly to morbidity and mortality in the surgical intensive care unit. Pulmonary embolism (PE) is a common and preventable cause of death in critically ill patients, with a mortality rate of up to 10%. Up to 95% of cases of PE originate from deep venous thrombosis (DVT). There are multiple pharmacologic and non-pharmacologic methods of DVT prophylaxis.The current standard of care in thromboprophylaxis in the surgical intensive care unit (SICU) at the University of Colorado Hospital is low-dose subcutaneous heparin (SCH). However, there is little evidence that this is the optimal prophylactic treatment. In fact, a database search of ICD-9 diagnoses made in 2005 suggests that the incidence of DVT in SICU patients, the majority who receive subcutaneous heparin, is approximately 7%. Surgical ICU patients are at high risk of developing DVT during their hospital stay and likely need more aggressive anticoagulation. Intravenous heparin, given at a low dose and titrated to a measurable endpoint PTT (partial thromboplastin time), may offer several benefits over the current standard of care, subcutaneous heparin. This method of treatment would offer more aggressive anticoagulation and allow dosage to be adjusted frequently based on each patient's changing coagulation status.

Study Design

• Study Type: Interventional
• Actual Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Efficacy of Low Dose Intravenous Heparin in Preventing Thromboembolism in the SICU.
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: continuous low dose intravenous heparin infusion titrated to a PTT of 40-45	Drug: low dose intravenous heparin (LDIVH); The LDIVH (experimental) group will receive a continuous heparin drip titrated to a prothrombin time (PTT) of 40-45. LDIVH subjects will have PTT tested within 24 hours prior to initiation of LDIVH. In addition, these subjects would continue to have a PTT tested every 6 hours until the PTT value falls between 40-45. All LDIVH subjects will have PTT values measured at least daily. This will continue until ICU discharge or a maximum of 28 days.
Active Comparator: subcutanous heparin 5000 units 3 times/day standard of care	Drug: Heparin; 5000 units given subcutaneously three times a day until ICU discharge or a maximum of 28 days

Outcome Measures

Primary Outcome Measures

1. Development of DVT (Deep Vein Thrombosis) [from start of study intervention to 6 months]

   In the first 70 patients, screening for DVT by ultrasound will occur on study days 0 and 5. After day 5 and for all remaining subjects, DVT will be diagnosed according to standard of care by the attending physician. Incidences of new DVT will be recorded daily until the patient is discharged from the hospital, or for a maximum of 28 days. DVT diagnosis will also be collected at 6 months from the primary care physician's office or the patient's household.

Secondary Outcome Measures

1. Development of PE's; Sepsis [up to 28 days post study intervention start]

   Secondary endpoints to be monitored for a maximum of 28 days, include: (1) total number of patients not developing PE; (2) total number of patients not developing sepsis; and (3) total number of patients not developing catheter-associated sepsis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• A signed informed consent;

• Age between 18 and 80 years

• The patient is admitted to the surgical intensive care unit at the University of Colorado Hospital

Exclusion Criteria:

• Predicated SICU stay less than 5 days;

• Pregnancy;

• Breast feeding;

• Initial platelet count < 30,000;

• Currently eligible for treatment of thromboembolism;

• Prior organ transplant;

• Cardiopulmonary bypass within previous 30 days;

• Advanced directive precluding participation;

• Already receiving pharmacologic agent for DVT prophylaxis;

• Prior diagnosis of heparin-induced thrombocytopenia;

• Heparin allergy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Hospital	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

• Principal Investigator: Sara Cheng, MD; PhD, University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT01608906
• Other Study ID Numbers: 06-0854
• First Posted: May 31, 2012
• Last Update Posted: Jul 29, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by University of Colorado, Denver: venous thrombosis; heparin; pulmonary embolism; ICU
• Additional relevant MeSH terms: Thrombosis; Venous Thrombosis; Heparin; Calcium heparin

Study Results

Participant Flow

Pre-assignment Detail	PI left the university in 2013. Numerous attempts were made to contact the PI and study team members, but efforts were unsuccessful. Arms are combined because no data is available regarding how participants were assigned to each study arm.

Arm/Group Title	All Participants
Arm/Group Description	Treatment: titrated to a PTT of 40-45. low dose intravenous heparin (LDIVH): The LDIVH (experimental) group will receive a continuous heparin drip titrated to a prothrombin time (PTT) of 40-45. LDIVH subjects will have PTT tested within 24 hours prior to initiation of LDIVH. In addition, these subjects would continue to have a PTT tested every 6 hours until the PTT value falls between 40-45. All LDIVH subjects will have PTT values measured at least daily. This will continue until ICU discharge or a maximum of 28 days. Control: Standard of Care.
Period Title: Overall Study
STARTED	152
COMPLETED	113
NOT COMPLETED	39

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Treatment: titrated to a PTT of 40-45. low dose intravenous heparin (LDIVH): The LDIVH (experimental) group will receive a continuous heparin drip titrated to a prothrombin time (PTT) of 40-45. LDIVH subjects will have PTT tested within 24 hours prior to initiation of LDIVH. In addition, these subjects would continue to have a PTT tested every 6 hours until the PTT value falls between 40-45. All LDIVH subjects will have PTT values measured at least daily. This will continue until ICU discharge or a maximum of 28 days. Control: Standard of Care.
Overall Participants	152
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	152 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	68 44.7%
Male	84 55.3%
Region of Enrollment (participants) [Number]
United States	152 100%

Outcome Measures

1. Primary Outcome

Title	Development of DVT (Deep Vein Thrombosis)
Description	In the first 70 patients, screening for DVT by ultrasound will occur on study days 0 and 5. After day 5 and for all remaining subjects, DVT will be diagnosed according to standard of care by the attending physician. Incidences of new DVT will be recorded daily until the patient is discharged from the hospital, or for a maximum of 28 days. DVT diagnosis will also be collected at 6 months from the primary care physician's office or the patient's household.
Time Frame	from start of study intervention to 6 months

Outcome Measure Data

Analysis Population Description

PI left the university in 2013. Numerous attempts were made to contact the PI and study team members, but efforts were unsuccessful. No outcome measure data is available

Arm/Group Title	Continuous Low Dose Intravenous Heparin Infusion	Subcutanous Heparin 5000 Units 3 Times/Day
Arm/Group Description	titrated to a PTT of 40-45 low dose intravenous heparin (LDIVH): The LDIVH (experimental) group will receive a continuous heparin drip titrated to a prothrombin time (PTT) of 40-45. LDIVH subjects will have PTT tested within 24 hours prior to initiation of LDIVH. In addition, these subjects would continue to have a PTT tested every 6 hours until the PTT value falls between 40-45. All LDIVH subjects will have PTT values measured at least daily. This will continue until ICU discharge or a maximum of 28 days.	standard of care Heparin: 5000 units given subcutaneously three times a day until ICU discharge or a maximum of 28 days
Measure Participants	0	0

2. Secondary Outcome

Title	Development of PE's; Sepsis
Description	Secondary endpoints to be monitored for a maximum of 28 days, include: (1) total number of patients not developing PE; (2) total number of patients not developing sepsis; and (3) total number of patients not developing catheter-associated sepsis.
Time Frame	up to 28 days post study intervention start

Outcome Measure Data

Analysis Population Description

PI left the university in 2013. Numerous attempts were made to contact the PI and study team members, but efforts were unsuccessful. No outcome measure data is available

Arm/Group Title	Continuous Low Dose Intravenous Heparin Infusion	Subcutanous Heparin 5000 Units 3 Times/Day
Arm/Group Description	titrated to a PTT of 40-45 low dose intravenous heparin (LDIVH): The LDIVH (experimental) group will receive a continuous heparin drip titrated to a prothrombin time (PTT) of 40-45. LDIVH subjects will have PTT tested within 24 hours prior to initiation of LDIVH. In addition, these subjects would continue to have a PTT tested every 6 hours until the PTT value falls between 40-45. All LDIVH subjects will have PTT values measured at least daily. This will continue until ICU discharge or a maximum of 28 days.	standard of care Heparin: 5000 units given subcutaneously three times a day until ICU discharge or a maximum of 28 days
Measure Participants	0	0

Adverse Events

Time Frame	6 Months.
Adverse Event Reporting Description	PI left the university in 2013. Numerous attempts were made to contact the PI and study team members, but efforts were unsuccessful. Arms are combined because no data is available regarding how participants were assigned to each study arm.
Arm/Group Title	All Participants
Arm/Group Description	Treatment: titrated to a PTT of 40-45. low dose intravenous heparin (LDIVH): The LDIVH (experimental) group will receive a continuous heparin drip titrated to a prothrombin time (PTT) of 40-45. LDIVH subjects will have PTT tested within 24 hours prior to initiation of LDIVH. In addition, these subjects would continue to have a PTT tested every 6 hours until the PTT value falls between 40-45. All LDIVH subjects will have PTT values measured at least daily. This will continue until ICU discharge or a maximum of 28 days. Control: Standard of Care.
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	0/152 (0%)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	0/152 (0%)
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	0/152 (0%)

Limitations/Caveats

PI left the university in 2013. Numerous attempts were made to contact the PI and study team members to obtain results data, but efforts were unsuccessful.

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.