Clinical trial NCT00853463: Discharge ALERT: Quality Improvement Initiative
Official title: Multi-centered Discharge Alert to Prevent DVT and PE at Hospital Discharge
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pulmonary Embolism
Deep Vein Thrombosis
Prophylaxis
Venous Thromboembolism
Prevention
Keywords: Pulmonary Embolism
Deep Vein Thrombosis
Prophylaxis
Venous thromboembolism
Prevention
Medical patients
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2009-03-02
Enrollment: 2515
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Brigham and Women's Hospital will coordinate a Quality Improvement Initiative at other hospitals that focuses on whether physician notification prior to discharge of high risk VTE patients will reduce the incidence of VTE after hospital discharge.

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 (1). North American and European prophylaxis guidelines have been widely disseminated. However, despite focus on strategies for the prevention of VTE in hospitalized patients at the time of admission to the hospital, there has been little focus on prevention of VTE at the time of discharge from the hospital (2,3).

At Brigham and Women's Hospital, we undertook a previous Quality Improvement Initiative (BWH protocol # 2000P000328) 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) randomizing high-risk patients without prophylaxis into an intervention group or control group. The intervention group's physicians received a single electronic, computerized alert explaining that the patient was at high risk, was not receiving prophylaxis, and suggesting that prophylaxis be ordered from a template of available pharmacological and mechanical options. In contrast, the control group's physicians received no alert (4).

Each of 8 common risk factors was weighted according to a point scale. To be labeled as "high-risk" for VTE, the point score must equal or exceed 4 points.

There were 2,506 patients in the Quality Improvement Initiative: 1,255 in the intervention group and 1,251 in the control group. The incidence of symptomatic VTE at 90 days was high: 8.2% in the control group and 4.9% in the intervention group (4).

Currently, an investigator initiated Quality Improvement Initiative (BWH protocol # 2005-P-002527) of human alerts rather than electronic, computerized alerts, has been undertaken in high risk patients not receiving prophylaxis. Enrollment of 2,500 patients at 25 centers located throughout the United States was completed in November 2007 with a follow-up rate that exceeded 99%. Analysis of the data is currently being conducted.

Limited research focus has been placed on high-risk VTE subjects in the community, outside of the hospital setting. Since most VTE prophylaxis has focused upon protection of high-risk patients at the time of hospital admission, there is a need to focus on VTE prophylaxis within 48 hours of hospital discharge. It is clear that as preparations are being made for hospital discharge, many patients remain at high risk for DVT and acute pulmonary embolism. After discharge, some patients will have an even higher risk than during hospitalization because of prolonged immobilization and bed rest at home (5).

The Discharge Alert Quality Improvement Initiative will determine whether alerting physicians about the importance of continued VTE prophylaxis just prior to the time of planned hospital discharge will lower the incidence of outpatient VTE. This new strategy is unproven and might not be effective, but this Quality Improvement Initiative should provide a definitive answer.

We will also implement as part of our Discharge Alert Trial an in-hospital Quality Improvement Initiative of intensive patient education at Brigham and Women's Hospital to improve patient adherence to physician-ordered pharmacological venous thromboembolism (VTE) prophylaxis. We hypothesize that after implementation of this education program, fewer patients will decline physician-ordered doses of enoxaparin or unfractionated heparin (UFH) compared with a recent cohort of patients at risk for VTE who did not receive specialized education about VTE.

METHODOLOGY

Identification of Patients at Risk for Venous Thromboembolism (VTE)

Hospitalized patients awaiting planned discharge within 48 hours will be evaluated with a previously validated (BWH protocol # 2000P000328) VTE risk profile. The VTE risk profile will be computed for each patient awaiting discharge using 8 common risk factors. Each risk factor is weighted according to a point score. To be labeled as "high risk" for VTE, 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, during this admission)

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

* Cancer (active)
* Prior VTE
* Hypercoagulability

Screening for Venous Thromboembolism Prophylaxis

If the cumulative VTE risk score is at least 4, 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.

At Brigham and Women's Hospital, we will also identify all new orders for pharmacological VTE prophylaxis with enoxaparin and UFH using the BWH computerized order entry system as part of an additional component of the Quality Improvement Initiative. For this component of the Quality Improvement Initiative, eligibility is defined as having a DVT Risk Score of 3 or higher and having electronically entered physician's orders for appropriate pharmacologic VTE thromboprophylaxis.

Quality Improvement Intervention

The intervention will take place within 48 hours of planned hospital discharge. If randomized to the alert, the responsible physician will be notified that: 1) his or her patient is at high risk for VTE, and 2) VTE prophylaxis should be considered in the Discharge orders. If randomized to no alert (control patients), the responsible physician will not be contacted.

At Brigham and Women's Hospital, we will also provide 500 eligible patients in a prospective cohort with one-on-one education using a scripted dialog to describe the rationale and importance of pharmacological VTE prophylaxis.

Prophylaxis Guidelines at Discharge

"Consider Venous Thromboembolism prophylaxis at the time of hospital discharge in patients with congestive heart failure or respiratory disease or prolonged immobility."

"For those without contraindication, consider pharmacological prophylaxis with low-molecular weight heparin, unfractionated heparin, or fondaparinux."

"For those at high risk of bleeding, consider mechanical prophylaxis with intermittent pneumatic compression devices or graduated compression stockings."

Follow Up

A 90-day follow-up will be performed for all study patients. If patient outcomes cannot be determined by medical record review alone, then study representatives may contact the subject's Primary Care Physician (PCP) for necessary information. IRB approval must be obtained at each participating hospital prior to any contact with subjects' PCPs.

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 90 and 30 days, respectively. These are the same endpoints utilized in our prior Quality Improvement Initiative (BWH protocol # 2000P000328).

Hemorrhagic events will be classified according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial criteria. Bleeding events will be classified as severe or life-threatening if they are intracerebral or if they result in substantial hemodynamic compromise requiring treatment. Moderate bleeding is defined by the need for transfusion. Minor events refer to bleeding not requiring transfusion or causing hemodynamic compromise. We will report rates of "major bleeding" which will be defined as GUSTO severe/life-threatening or moderate bleeding.

For the additional component of the Quality Improvement Initiative at Brigham and Women's Hospital, we will also assess improvement of medication adherence with enoxaparin and UFH following an intensive and individualized patient education program compared with our recently completed cohort study in which no uniform education program was targeted at VTE prophylaxis.

Statistical Analysis

The initial sample size (power 80%, two-sided alpha 5%) has been calculated at 2,500 patients based on an estimated 7% rate of the primary end point in the control group, and an odds ratio of 0.59 for the primary endpoint in intervention group patients. This yields a sample size requirement of 2,138 patients, plus an estimated 362 patients who will withdraw from the study.

We will use Wilcoxon rank-sum tests for comparisons in the distributions of continuous variables between groups, and chi-square tests or Fisher's exact test for comparisons of categorical variables. The primary analysis is the difference in the Kaplan-Meier estimator for freedom from VTE at day 90 between intervention and control patients. The log-rank test will estimate the cumulative probability of the primary endpoint in the intervention and control groups. We will use the proportional-hazards model for estimation of the relative hazard of clinical endpoints associated with the physician alert. All p-values reported are two-sided.

Eligibility criteria: Inclusion Criteria:

* Patients \> 18 years of age
* Planned discharge within 48 hours
* Cumulative VTE risk score at least 4
* Patients from Medical Services

Exclusion Criteria:

* VTE risk score \<4
* Patients \<18 years of age
* Full anticoagulation therapy planned upon discharge, i.e., atrial fibrillation, mechanical heart valve, venous thromboembolism treatment, etc.
* Patient is admitted to a non-medical service, i.e., surgical service, orthopedics, obstetrics/gynecology, neurology, psychiatry, or other non-medical service

Primary outcomes:
measure: Clinically diagnosed DVT and/or PE
timeFrame: 90 days after discharge
Secondary outcomes:
measure: Mortality
timeFrame: 30 and 90 days
measure: Hemorrhagic events
timeFrame: 30 and 90 days
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach VA Healthcare System
state: California
city: Orange
country: United States
facility: UC Irvine
state: California
city: Sacramento
country: United States
facility: UC Davis
state: California
city: Denver
country: United States
facility: Denver VA Medical Center
state: Colorado
city: Norwich
country: United States
facility: William Backus Hospital
state: Connecticut
city: Baltimore
country: United States
facility: Medstar Research Frankin Square Hospital
state: Maryland
city: Hagerstown
country: United States
facility: Washington County Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Salem
country: United States
facility: North Shore Medical Center
state: Massachusetts
city: Ypsilanti
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Columbia
country: United States
facility: University of Missouri- Columbia
state: Missouri
city: St. Louis
country: United States
facility: St. John's Mercy Medical Center
state: Missouri
city: Albuquerque
country: United States
facility: Lovelace Medical Center
state: New Mexico
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Indiana
country: United States
facility: Indiana Regional Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson Hospital
state: Pennsylvania
city: Washington
country: United States
facility: Washington Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: Presbyterian Hospital Texas Health
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: Intermountain Medical Center
state: Utah
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: Spencer FA, Lessard D, Emery C, Reed G, Goldberg RJ. Venous thromboembolism in the outpatient setting. Arch Intern Med. 2007 Jul 23;167(14):1471-5. doi: 10.1001/archinte.167.14.1471.