Clinical trial NCT00409136: Multi-Center Human Alert Trial to Prevent DVT and PE
Official title: Physician Alerts to Prevent DVT and Pulmonary Embolism in Hospitalized Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pulmonary Embolism
Deep Vein Thrombosis
Cancer
Surgery
Keywords: Alert
Deep Vein Thrombosis
Pulmonary Embolism
Venous Thromboembolism
Prophylaxis
Anticoagulation
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2006-12-08
Enrollment: 2496
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Hospitalized patients that have a cumulative VTE risk score of 4 or more with no orders for prophylactic measures.

Brief summary: To evaluate physician response to human alerts that inform the clinician that his/her patient may be eligible for thromboprophylaxis. Medical records are reviewed to evaluate prescribing decision and to evaluate rates of venous thromboembolism.

Detailed description: Background Information and Rationale for the Study:

Venous thromboembolism (VTE) is often avoidable in hospitalized patients because proven prevention strategies have been established for patients at risk. North American and European prophylaxis guidelines have been widely disseminated. However, despite intensive educational efforts, VTE prevention remains underutilized.

At Brigham and Women's Hospital, we undertook a comprehensive program aimed at increasing the frequency of VTE prophylaxis in high risk patients. This novel strategy required: 1) devising a risk score that reliably and quickly identified patients at high risk of VTE, and 2) conducting a randomized controlled trial in which high risk patients without prophylaxis were randomized into an intervention or control group. The intervention group's physicians received a single alert explaining that the patient was at high risk, was not receiving prophylaxis, and urged that prophylaxis be selected from a template of available pharmacological and mechanical options. In contrast, the control group's physicians received no alert.

Each of 8 common risk factors was weighted according to a point scale. At least 4 score points were required to be deemed at "high risk" for VTE.

3 of the 8 risk factors were considered major and were assigned a score of 3 points each:

1. Cancer
2. Prior VTE
3. Hypercoagulability

One of the 8 risk factors, surgery, was considered intermediate and was assigned a score of 2.

4 of the 8 risk factors were considered minor and were assigned a score of 1 point each:

1. Advanced age (\> 70 years of age)
2. Obesity (Body Mass Index \> 29)
3. Bed rest
4. Hormone replacement therapy or oral contraceptives

There were 2,506 patients in the randomized controlled trial of a computer alert: 1255 in the intervention group and 1251 in the control group. The incidence of symptomatic VTE at 90 days was high: 8.2% in the control group. This high incidence validates the 8 risk factor and point score methodology.

The intervention group had an overall 41% reduction in VTE, without any increase in major bleeding. There was a 60% reduction in the incidence of symptomatic pulmonary embolism.

Identification of Patients at Risk for Venous Thromboembolism (VTE):

A VTE risk profile will be computed for each hospitalized patient using 8 common risk factors. Each risk factor is weighted according to a point score. To be included in this trial, the point score must equal or exceed 4 points.

Minor (Low) Risk Factors (1 POINT each):

* Advanced Age (\>70 years of age)
* Obesity (BMI \>29, or the presence of the word "obesity" in admission exam notes)
* Bed rest / Immobility (not related to surgery)
* Female Hormone Replacement Therapy or Oral Contraceptives

Intermediate Risk Factor (2 POINTS each):

· Major Surgery (\> 60 minutes)

Major (High) Risk Factors (3 POINTS each):

* Cancer (active)
* Prior VTE
* Hypercoagulability

Increased VTE risk is defined as a cumulative VTE risk score 4, so that patients with at least 1 major risk factor (cancer, prior VTE, or hypercoagulability) plus at least 1 additional intermediate risk factor (major surgery or bed rest) or minor risk factor (advanced age, obesity, or hormone replacement therapy/oral contraceptives) become eligible. In the absence of a major risk factor, patients with 1 intermediate risk factor plus at least 2 minor risk factors become eligible.

Screening for Venous Thromboembolism Prophylaxis:

If the cumulative VTE risk score is ³4, orders are reviewed to detect ongoing mechanical or pharmacological prophylactic measures. Mechanical prophylactic measures include graduated compression stockings and intermittent pneumatic compression devices. Pharmacological prophylactic measures include unfractionated heparin, enoxaparin, dalteparin, fondaparinux, tinzaparin, and warfarin.

Randomization:

Randomization Envelopes containing the statement "ALERT" (Intervention) or "NO ALERT" (Control) will be provided by Harvard Clinical Research Institute (HCRI), to randomize patients who meet all inclusion criteria.

The intervention is informing the responsible physician that: 1) his or her patient is at high risk for VTE, 2) is not receiving prophylaxis, and 3) VTE prophylaxis is recommended. For control patients, VTE prevention guidelines are available, but no specific prompt is provided to use them.

Follow Up:

Ninety-day follow-up is performed in all study patients by medical record review and through contact with the subject's Primary Care Physician.

Data Collection and Study Endpoints:

The primary endpoint is clinically diagnosed DVT or PE at 90 days. Safety endpoints include total mortality and hemorrhagic events at 30 and 90 days, respectively. We define major bleeding as intracranial, intraocular, retroperitoneal, pericardial, or bleeding that requires surgical intervention or that resulted in a hemoglobin loss greater than 3 g/l.

DVT is diagnosed if there is loss of vein compressibility by ultrasound or a filling defect by CT scan or by conventional contrast venography. PE is diagnosed by a positive contrast chest CT scan, a high-probability ventilation perfusion scan, or conventional pulmonary angiogram.

Eligibility criteria: Inclusion Criteria:

* Patients \> 18 years of age
* Cumulative VTE risk score \> 4
* Absence of pharmacologic or mechanical prophylaxis orders
* Patients from medical or surgical Services

Exclusion Criteria:

* VTE risk score \<4
* Current active pharmacologic or mechanical prophylaxis order
* Patients from the Department of Neurology, Newborn Service, Rehab Units, and Neonatal Intensive Care Unit (NICU).

Primary outcomes:
measure: Clinically diagnosed DVT and/or PE
timeFrame: 90 days
Secondary outcomes:
measure: Mortality
timeFrame: 30 and 90 days
measure: Hemorrhagic events
timeFrame: 30 and 90 days
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: AZ Pulmonary Specialists, Ltd
state: Arizona
city: Long Beach
country: United States
facility: Long Beach VA Hospital
state: California
city: Orange
country: United States
facility: University of California - Irvine
state: California
city: Sacramento
country: United States
facility: University of California - Davis
state: California
city: Denver
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Norwich
country: United States
facility: William W. Backus Hospital
state: Connecticut
city: Washington DC
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory-Crawford Long Hospital
state: Georgia
city: Baltimore
country: United States
facility: Franklin Square Hospital
state: Maryland
city: Hagerstown
country: United States
facility: Washington County Hospital
state: Maryland
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Salem
country: United States
facility: North Shore Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital K15
state: Michigan
city: Ypsilanti
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Great Neck
country: United States
facility: North Shore University Hospital
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson Hospital
state: Pennsylvania
city: Washington
country: United States
facility: Washington Hospital
state: Pennsylvania
city: Spartanburg
country: United States
facility: Spartanburg Regional Medical Center
state: South Carolina
city: Dallas
country: United States
facility: Presbyterian Hospital of Dallas
state: Texas
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
city: Kenosha
country: United States
facility: United Hospital System
state: Wisconsin
Study officials:
affiliation: Brigham and Women's Hospital
name: Samuel Z. Goldhaber, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Goldhaber SZ, Turpie AG. Prevention of venous thromboembolism among hospitalized medical patients. Circulation. 2005 Jan 4;111(1):e1-3. doi: 10.1161/01.CIR.0000150393.51958.54. No abstract available.
citation: Goldhaber SZ, Dunn K, MacDougall RC. New onset of venous thromboembolism among hospitalized patients at Brigham and Women's Hospital is caused more often by prophylaxis failure than by withholding treatment. Chest. 2000 Dec;118(6):1680-4. doi: 10.1378/chest.118.6.1680.
citation: Goldhaber SZ, Tapson VF; DVT FREE Steering Committee. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol. 2004 Jan 15;93(2):259-62. doi: 10.1016/j.amjcard.2003.09.057.
citation: Kucher N, Koo S, Quiroz R, Cooper JM, Paterno MD, Soukonnikov B, Goldhaber SZ. Electronic alerts to prevent venous thromboembolism among hospitalized patients. N Engl J Med. 2005 Mar 10;352(10):969-77. doi: 10.1056/NEJMoa041533.
citation: Piazza G, Rosenbaum EJ, Pendergast W, Jacobson JO, Pendleton RC, McLaren GD, Elliott CG, Stevens SM, Patton WF, Dabbagh O, Paterno MD, Catapane E, Li Z, Goldhaber SZ. Physician alerts to prevent symptomatic venous thromboembolism in hospitalized patients. Circulation. 2009 Apr 28;119(16):2196-201. doi: 10.1161/CIRCULATIONAHA.108.841197. Epub 2009 Apr 13.