Multi-Center Human Alert Trial to Prevent DVT and PE

Physician Alerts to Prevent DVT and Pulmonary Embolism in Hospitalized Patients

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.

Study Overview

• Status: Completed
• Conditions: Cancer; Surgery; Deep Vein Thrombosis; Pulmonary Embolism
• Intervention / Treatment: Behavioral: Human Alert

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.

• Study Type: Observational
• Enrollment (Actual): 2496

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • AZ Pulmonary Specialists, Ltd
  • California
    • Long Beach, California, United States, 90822
      • Long Beach VA Hospital
    • Orange, California, United States, 92868
      • University of California - Irvine
    • Sacramento, California, United States, 95817
      • University of California - Davis
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado Health Sciences Center
  • Connecticut
    • Norwalk, Connecticut, United States, 06850
      • Norwalk Hospital
    • Norwich, Connecticut, United States, 06360
      • William W. Backus Hospital
  • District of Columbia
    • Washington DC, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Orlando, Florida, United States, 32803
      • Florida Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory-Crawford Long Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Franklin Square Hospital
    • Hagerstown, Maryland, United States, 21740
      • Washington County Hospital
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic
    • Salem, Massachusetts, United States, 01970
      • North Shore Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital K15
    • Ypsilanti, Michigan, United States, 48197
      • St. Joseph Mercy Hospital
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri
  • New York
    • Great Neck, New York, United States, 11030
      • North Shore University Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson Hospital
    • Washington, Pennsylvania, United States, 15301
      • Washington Hospital
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Regional Medical Center
  • Texas
    • Dallas, Texas, United States, 75231
      • Presbyterian Hospital of Dallas
  • Utah
    • Salt Lake City, Utah, United States, 84103
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Medical Center
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53143
      • United Hospital System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Alert; Physicians alerted about their high risk patients who are not receiving any VTE prophylaxis.	Behavioral: Human Alert; An alert from study staff informing a physician that his/her patient is at high risk for DVT and/or PE, but is not receiving any prophylaxis.
No Alert; Physicians not alerted about their high risk patients who are not receiving any VTE prophylaxis.	Behavioral: Human Alert; An alert from study staff informing a physician that his/her patient is at high risk for DVT and/or PE, but is not receiving any prophylaxis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinically diagnosed DVT and/or PE	90 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality	30 and 90 days
Hemorrhagic events	30 and 90 days

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Sanofi
• Investigators: Principal Investigator: Samuel Z. Goldhaber, MD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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. Erratum In: Circulation. 2010 Jul 6;122(1):e4.

Helpful Links

• North American Thrombosis Forum

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: December 7, 2006
• First Submitted That Met QC Criteria: December 7, 2006
• First Posted (Estimate): December 8, 2006

Study Record Updates

• Last Update Posted (Estimate): February 2, 2009
• Last Update Submitted That Met QC Criteria: January 29, 2009
• Last Verified: January 1, 2009

More Information

Terms related to this study

• Keywords: Anticoagulation; Deep Vein Thrombosis; Venous Thromboembolism; Prophylaxis; Pulmonary Embolism; Alert
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Pulmonary Embolism
• Other Study ID Numbers: 2005-P-002527