Pilot Study of Bevacizumab (Avastin) in Patients With Septic Shock

NCT01063010 | Withdrawn DMC

• 1 other identifier: 2009000036
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to perform a pilot study to assess the potential use of Bevacizumab (a vascular endothelial growth factor (VEGF) inhibitor) in sepsis.

Conditions

Septic Shock

Keywords

sepsis; septic shock; Bevacizumab; Avastin

Outcome Measures

Primary Outcomes (1)

• The change in Sequential Organ Failure Assessment score (SOFA) to assess reduction in organ failure

  Between 0 and 72 hours

Secondary Outcomes (5)

• Inflammation signaling: the change in circulating levels of IL-6 and TNF-alpha level as the primary

  1, 2, 3, 5, 7 and 28 days

• Endothelial cell signaling/activation: change in E-selectin, ICAM-1, and sFLT

  1, 2, 3, 5, 7, 28 days

• VEGF signaling: measurement of VEGF levels in response to the study drug or placebo and determine if there is a reduction in overall VEGF signaling.

  1, 2, 3, 5, 7, 28 days

• Overall safety of Bevacizumab

  Through Day 60

• Mortality

  In hospital

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo IV for 90 minutes (+ 15 minutes)

Drug: Placebo

Bevicizumab

EXPERIMENTAL

IV infusion over 90 minutes

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

Administered intravenously 10 mg/kg over 90 minutes (+ 15 minutes)

Also known as: Avastin

Bevicizumab

Placebo DRUG

Placebo administered intravenously for 90 minutes (+ 15 minutes)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Evidence of infection a. temperature \> 100.4F or \< 97.0F of non-environmental causes, pneumonia as determined by the presence of an infiltrate on chest x-ray, a non-contaminated urinalysis with \> 10 WBC or a urine dip-stick positive for leukocyte esterase, an abdominal CT scan yielding the diagnosis of an intra-abdominal etiology, skin/soft tissue infection on clinical exam.
• Two or more SIRS criteria a. tachycardia (HR\>90) b. tachypnea (RR\>20) or hypoxia (oxygen saturation\<90%) c. hyperthermia \>100.4 F (38C) or hypothermia \<96F (35.5C) d. leukocytosis WBC\> 15,000 cells/mm3 or bands\>10%\]
• Septic shock a. persistent hypotension (SBP \< 90mmHg) after an initial 20-30 cc/kg fluid challenge, or the need for vasopressors for at least 1 hour in order to maintain a systolic blood pressure \>90 mmHG; enrollment within 48 hours of meeting eligibility criteria.

You may not qualify if:

• Life expectancy of less than 12 weeks
• Inadequately controlled hypertension
• Prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
• History of myocardial infarction or unstable angina within 12 months prior to Day 1
• History of stroke or transient ischemic attack within 12 months prior to Day 1
• Known CNS malignancy, except for treated brain metastasis
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
• History of hemoptysis within 1 month prior to Day 1
• History of chronic bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
• History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
• Serious, non-healing wound, active ulcer, or untreated bone fracture
• Proteinuria at screening

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• The Cooper Health System: collaborator
• Carolinas Medical Center: collaborator

Study Sites (3)

Beth Israel Medical Center

Boston, Massachusetts, 02215, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Related Publications (1)

• Shapiro NI, Aird WC. Sepsis and the broken endothelium. Crit Care. 2011 Mar 21;15(2):135. doi: 10.1186/cc10044.

  PMID: 21457513 DERIVED

MeSH Terms

Conditions

Shock, Septic; Sepsis

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nathan I Shapiro, MD

  Beth Israel Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Emergency Medicine

Study Record Dates

• First Submitted: February 3, 2010
• First Posted: February 5, 2010
• Study Start: February 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: October 29, 2024

Record last verified: 2024-10

Locations

US (3)