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

This study has been withdrawn prior to enrollment.
(No funding)
Sponsor:
Information provided by:
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT01314066
First received: July 28, 2010
Last updated: March 10, 2011
Last verified: March 2011
  Purpose

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.


Condition Intervention Phase
Severe Sepsis
Acute Respiratory Distress Syndrome
Drug: Bevacizumab
Drug: Placebo IV Solution
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Efficacy of Bevacizumab in Preventing Acute Respiratory Distress Syndrome (ARDS)

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

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. [ Time Frame: Day 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Ventilator-free days to Day 28 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • 28 day all-cause mortality [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Proportion of subjects progressing to acute lung injury (who do not meet the definition at randomization) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Worst PaO2/FiO2 ratio recorded following enrollment [ Time Frame: Day 3 and 28 ] [ Designated as safety issue: No ]
  • Change in PaO2/FiO2 ratio between Day 0 to Day 3 [ Time Frame: Day 0 and Day 3 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Proportion of subjects surviving to hospital discharge [ Time Frame: Hospital Discharge Day ] [ Designated as safety issue: No ]
  • Vasopressor-free days [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Reversal of shock if present at randomization. [ Time Frame: Day 28 ] [ Designated as safety issue: No ]

Estimated Enrollment: 75
Study Start Date: July 2010
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 IV Solution
Patients assigned to placebo-control group will receive a single dose of saline solution as a 90 minute IV infusion

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01314066

Locations
United States, New York
Weill Cornell Medical College-New York Presbyterian Hospital
New York, New York, United States, 10065
Sponsors and Collaborators
Weill Medical College of Cornell University
  More Information

Publications:

Responsible Party: Robert J. Kaner, MD, Weill Cornell Medical College
ClinicalTrials.gov Identifier: NCT01314066     History of Changes
Other Study ID Numbers: IRB Protocol #0907010498
Study First Received: July 28, 2010
Last Updated: March 10, 2011
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Sepsis
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014