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

April 29, 2016 updated by: Weill Medical College of Cornell University
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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Weill Cornell Medical College-New York Presbyterian Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Bevacizumab 5 mg/kg
Receive drug solution as a single dose. Treatment will be given as 90 minute IV infusion.
Drug: Bevacizumab
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.
Other Names:
  • Avastin
EXPERIMENTAL: Bevacizumab at 10 mg/kg
Receive drug solution as a single dose. Treatment will be given as 90 minute IV infusion.
Drug: Bevacizumab
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.
Other Names:
  • Avastin
PLACEBO_COMPARATOR: Placebo
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.
Drug: Placebo
Patients assigned to placebo-control group will receive a single dose of saline solution as a 90 minute IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Day 28

Secondary Outcome Measures

Outcome Measure
Time Frame
Ventilator-free days to Day 28
Time Frame: Day 28
Day 28
28 day all-cause mortality
Time Frame: Day 28
Day 28
Proportion of subjects progressing to acute lung injury (who do not meet the definition at randomization)
Time Frame: Day 28
Day 28
Worst PaO2/FiO2 ratio recorded following enrollment
Time Frame: Day 3 and 28
Day 3 and 28
Change in PaO2/FiO2 ratio between Day 0 to Day 3
Time Frame: Day 0 and Day 3
Day 0 and 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
Time Frame: Day 0, Day 28
Day 0, Day 28
Proportion of subjects surviving to hospital discharge
Time Frame: Hospital Discharge Day
Hospital Discharge Day
Vasopressor-free days
Time Frame: Day 28
Day 28
Reversal of shock if present at randomization.
Time Frame: Day 28
Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Weill Medical College of Cornell University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2010

Primary Completion (ANTICIPATED)

November 1, 2015

Study Completion (ANTICIPATED)

February 1, 2016

Study Registration Dates

First Submitted

July 28, 2010

First Submitted That Met QC Criteria

March 10, 2011

First Posted (ESTIMATE)

March 14, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

May 3, 2016

Last Update Submitted That Met QC Criteria

April 29, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB Protocol #0907010498

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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