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Efficacy of Bevacizumab in Preventing Acute Respiratory Distress Syndrome (ARDS) (VEGF-ARDS)

Primary Purpose

Severe Sepsis, Acute Respiratory Distress Syndrome

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bevacizumab
Placebo
Sponsored by
Weill Medical College of Cornell University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Severe Sepsis

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Clinical Diagnosis of Sepsis based on Modified Inflammatory Response Syndrome (SIRS) Criteria
  • Evidence of a systemic response to infection
  • 1 or more sepsis-induced organ failures modified from those as defined by Bernard, et al. (eg. PROWESS rhAPC study, NEJM)

Exclusion Criteria:

  • Pregnant females
  • Systolic blood pressure >170
  • Diastolic blood pressure >110
  • Preexisting proteinuria >0.3 g/24hr
  • Known hypersensitivity to bevacizumab
  • Subject or health care agent unable to provide written informed consent
  • Diagnosis of lung cancer with active hemoptysis
  • Patient not expected to survive 28 days independently of the septic episode due to severe underlying disease
  • Presence of an advanced directive to withhold life-sustaining treatment
  • Participation in another investigational study within 30 days of enrollment
  • GI tract perforation and/or repair unless surgical incision is fully healed
  • Any major surgery in the 28 days prior to enrollment
  • Need for non-elective major surgery within 28 days
  • Presence of enterocutaneous fistula (an abnormal connection between body cavities, in this case, from the intestine to the skin. Possible complication of surgery, where passageway progresses from intestine to surgery site to skin)
  • Known or suspected tracheoesophageal fistula (an abnormal connection between the esophagus and the trachea)
  • Current ICU stay of > 2 months prior to enrollment
  • Need for therapeutic anti-coagulation

Sites / Locations

  • Weill Cornell Medical College-New York Presbyterian Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Bevacizumab 5 mg/kg

Bevacizumab at 10 mg/kg

Placebo

Arm Description

Receive drug solution as a single dose. Treatment will be given as 90 minute IV infusion.

Receive drug solution as a single dose. Treatment will be given as 90 minute IV infusion.

In addition to receiving the best standard supportive care for both diagnosis and treatment for individuals diagnosed with severe sepsis, they will receive an IV saline solution.

Outcomes

Primary Outcome Measures

Proportion of individuals progressing to meet RDS criteria as defined by the American- European ARDS consensus conference and as used by ARDSnet.

Secondary Outcome Measures

Ventilator-free days to Day 28
28 day all-cause mortality
Proportion of subjects progressing to acute lung injury (who do not meet the definition at randomization)
Worst PaO2/FiO2 ratio recorded following enrollment
Change in PaO2/FiO2 ratio between Day 0 to Day 3
Change from baseline in number of non-lung organ failures using the Multi-Organ Dysfunction (MOD) score and Sepsis Organ Failure Assessment (SOFA) score
Proportion of subjects surviving to hospital discharge
Vasopressor-free days
Reversal of shock if present at randomization.

Full Information

First Posted
July 28, 2010
Last Updated
April 29, 2016
Sponsor
Weill Medical College of Cornell University
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1. Study Identification

Unique Protocol Identification Number
NCT01314066
Brief Title
Efficacy of Bevacizumab in Preventing Acute Respiratory Distress Syndrome (ARDS)
Acronym
VEGF-ARDS
Official Title
Efficacy of Bevacizumab in Preventing Acute Respiratory Distress Syndrome (ARDS)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2016
Overall Recruitment Status
Withdrawn
Why Stopped
No funding
Study Start Date
July 2010 (undefined)
Primary Completion Date
November 2015 (Anticipated)
Study Completion Date
February 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study aims to test the effectiveness of a single intravenous (IV, through the vein) dose of the study drug, bevacizumab (Avastin), in preventing/reducing the development of Acute Respiratory Distress Syndrome (ARDS), in patients with severe sepsis, who are at high risk for developing ARDS. ARDS is a lung disease caused by a lung injury that leads to lung function impairment. The condition the patient has,severe sepsis, is a medical condition associated with an infection characterized as an immune system inflammatory response throughout your whole body that can lead to organ dysfunction, low blood pressure or insufficient blood flow to one or more of your organs.
Detailed Description
Acute respiratory distress syndrome (ARDS) is the most extreme form of acute lung injury (ALI) that results in a loss of lung function and structure. Vascular endothelial growth factor (VEGF), a protein critical for lung development that is found in the thin layer of liquid lining the inner surface of the lung air sacs, is believed to play a key role in the development of ARDS. During ARDS/ALI, VEGF markedly increases the permeability of the cells lining the inner surface of blood vessels in the lungs, which leads to an accumulation of fluid in the lungs (pulmonary edema), a characteristic of ARDS/ALI. Thus, anti-VEGF therapies offer a unique approach to treat this potentially fatal disorder. Bevacizumab (Avastin ®), an anti-VEGF medication, has been shown to be effective in inhibiting pulmonary edema caused by VEGF over-expression in an animal model. This study will establish the usefulness and effectiveness of a singe dose of Bevacizumab administered intravenously (through the vein) in reducing the incidence of ARDS in individuals with severe sepsis (a condition characterized by an inflammatory response by the immune system throughout the whole body caused by infection) who are at high risk for the development of ARDS. All study participants will be randomized to receive placebo, bevacizumab 5 mg/kg or bevacizumab 10 mg/kg as a single intravenous dose in a double-blinded fashion in addition to traditional sepsis treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Sepsis, Acute Respiratory Distress Syndrome

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bevacizumab 5 mg/kg
Arm Type
Experimental
Arm Description
Receive drug solution as a single dose. Treatment will be given as 90 minute IV infusion.
Arm Title
Bevacizumab at 10 mg/kg
Arm Type
Experimental
Arm Description
Receive drug solution as a single dose. Treatment will be given as 90 minute IV infusion.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
In addition to receiving the best standard supportive care for both diagnosis and treatment for individuals diagnosed with severe sepsis, they will receive an IV saline solution.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Patients receiving drug will receive it as a single dose. Treatment will be given as 90-minute IV infusion. The patient will either receive Bevacizumab at 5 mg/kg OR Bevacizumab at 10 mg/kg.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Patients assigned to placebo-control group will receive a single dose of saline solution as a 90 minute IV infusion
Primary Outcome Measure Information:
Title
Proportion of individuals progressing to meet RDS criteria as defined by the American- European ARDS consensus conference and as used by ARDSnet.
Time Frame
Day 28
Secondary Outcome Measure Information:
Title
Ventilator-free days to Day 28
Time Frame
Day 28
Title
28 day all-cause mortality
Time Frame
Day 28
Title
Proportion of subjects progressing to acute lung injury (who do not meet the definition at randomization)
Time Frame
Day 28
Title
Worst PaO2/FiO2 ratio recorded following enrollment
Time Frame
Day 3 and 28
Title
Change in PaO2/FiO2 ratio between Day 0 to Day 3
Time Frame
Day 0 and Day 3
Title
Change from baseline in number of non-lung organ failures using the Multi-Organ Dysfunction (MOD) score and Sepsis Organ Failure Assessment (SOFA) score
Time Frame
Day 0, Day 28
Title
Proportion of subjects surviving to hospital discharge
Time Frame
Hospital Discharge Day
Title
Vasopressor-free days
Time Frame
Day 28
Title
Reversal of shock if present at randomization.
Time Frame
Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Clinical Diagnosis of Sepsis based on Modified Inflammatory Response Syndrome (SIRS) Criteria Evidence of a systemic response to infection 1 or more sepsis-induced organ failures modified from those as defined by Bernard, et al. (eg. PROWESS rhAPC study, NEJM) Exclusion Criteria: Pregnant females Systolic blood pressure >170 Diastolic blood pressure >110 Preexisting proteinuria >0.3 g/24hr Known hypersensitivity to bevacizumab Subject or health care agent unable to provide written informed consent Diagnosis of lung cancer with active hemoptysis Patient not expected to survive 28 days independently of the septic episode due to severe underlying disease Presence of an advanced directive to withhold life-sustaining treatment Participation in another investigational study within 30 days of enrollment GI tract perforation and/or repair unless surgical incision is fully healed Any major surgery in the 28 days prior to enrollment Need for non-elective major surgery within 28 days Presence of enterocutaneous fistula (an abnormal connection between body cavities, in this case, from the intestine to the skin. Possible complication of surgery, where passageway progresses from intestine to surgery site to skin) Known or suspected tracheoesophageal fistula (an abnormal connection between the esophagus and the trachea) Current ICU stay of > 2 months prior to enrollment Need for therapeutic anti-coagulation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Kaner, MD
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Weill Cornell Medical College-New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
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Efficacy of Bevacizumab in Preventing Acute Respiratory Distress Syndrome (ARDS)

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