Acute Respiratory Distress Syndrome Clinical Trial
— VEGF-ARDSOfficial title:
Efficacy of Bevacizumab in Preventing Acute Respiratory Distress Syndrome (ARDS)
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.
Status | Withdrawn |
Enrollment | 0 |
Est. completion date | February 2016 |
Est. primary completion date | November 2015 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 99 Years |
Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention
Country | Name | City | State |
---|---|---|---|
United States | Weill Cornell Medical College-New York Presbyterian Hospital | New York | New York |
Lead Sponsor | Collaborator |
---|---|
Weill Medical College of Cornell University |
United States,
Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):818-24. Review. — View Citation
Hao Q, Wang L, Tang H. Vascular endothelial growth factor induces protein kinase D-dependent production of proinflammatory cytokines in endothelial cells. Am J Physiol Cell Physiol. 2009 Apr;296(4):C821-7. doi: 10.1152/ajpcell.00504.2008. Epub 2009 Jan 28. — View Citation
Kaner RJ, Crystal RG. Compartmentalization of vascular endothelial growth factor to the epithelial surface of the human lung. Mol Med. 2001 Apr;7(4):240-6. — View Citation
Kaner RJ, Crystal RG. Pathogenesis of high altitude pulmonary edema: does alveolar epithelial lining fluid vascular endothelial growth factor exacerbate capillary leak? High Alt Med Biol. 2004 Winter;5(4):399-409. Review. — View Citation
Kaner RJ, Ladetto JV, Singh R, Fukuda N, Matthay MA, Crystal RG. Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema. Am J Respir Cell Mol Biol. 2000 Jun;22(6):657-64. — View Citation
National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006 Jun 15;354(24):2564-75. Epub 2006 May 21. — View Citation
Nolan A, Weiden MD, Thurston G, Gold JA. Vascular endothelial growth factor blockade reduces plasma cytokines in a murine model of polymicrobial sepsis. Inflammation. 2004 Oct;28(5):271-8. — View Citation
Pepe PE, Potkin RT, Reus DH, Hudson LD, Carrico CJ. Clinical predictors of the adult respiratory distress syndrome. Am J Surg. 1982 Jul;144(1):124-30. — View Citation
Phua J, Badia JR, Adhikari NK, Friedrich JO, Fowler RA, Singh JM, Scales DC, Stather DR, Li A, Jones A, Gattas DJ, Hallett D, Tomlinson G, Stewart TE, Ferguson ND. Has mortality from acute respiratory distress syndrome decreased over time?: A systematic review. Am J Respir Crit Care Med. 2009 Feb 1;179(3):220-7. doi: 10.1164/rccm.200805-722OC. Epub 2008 Nov 14. Review. — View Citation
Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD. Incidence and outcomes of acute lung injury. N Engl J Med. 2005 Oct 20;353(16):1685-93. — View Citation
Shapiro NI, Yano K, Okada H, Fischer C, Howell M, Spokes KC, Ngo L, Angus DC, Aird WC. A prospective, observational study of soluble FLT-1 and vascular endothelial growth factor in sepsis. Shock. 2008 Apr;29(4):452-7. — View Citation
Tsao PN, Chan FT, Wei SC, Hsieh WS, Chou HC, Su YN, Chen CY, Hsu WM, Hsieh FJ, Hsu SM. Soluble vascular endothelial growth factor receptor-1 protects mice in sepsis. Crit Care Med. 2007 Aug;35(8):1955-60. — View Citation
van der Flier M, van Leeuwen HJ, van Kessel KP, Kimpen JL, Hoepelman AI, Geelen SP. Plasma vascular endothelial growth factor in severe sepsis. Shock. 2005 Jan;23(1):35-8. — View Citation
Wakelee H. Antibodies to vascular endothelial growth factor in non-small cell lung cancer. J Thorac Oncol. 2008 Jun;3(6 Suppl 2):S113-8. doi: 10.1097/JTO.0b013e318174e993. Review. — View Citation
Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1334-49. Review. — View Citation
Watanabe M, Boyer JL, Crystal RG. Genetic delivery of bevacizumab to suppress vascular endothelial growth factor-induced high-permeability pulmonary edema. Hum Gene Ther. 2009 Jun;20(6):598-610. doi: 10.1089/hum.2008.169. — View Citation
Watanabe M, Boyer JL, Hackett NR, Qiu J, Crystal RG. Genetic delivery of the murine equivalent of bevacizumab (avastin), an anti-vascular endothelial growth factor monoclonal antibody, to suppress growth of human tumors in immunodeficient mice. Hum Gene Ther. 2008 Mar;19(3):300-10. doi: 10.1089/hum.2007.109. — View Citation
Yano K, Liaw PC, Mullington JM, Shih SC, Okada H, Bodyak N, Kang PM, Toltl L, Belikoff B, Buras J, Simms BT, Mizgerd JP, Carmeliet P, Karumanchi SA, Aird WC. Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality. J Exp Med. 2006 Jun 12;203(6):1447-58. Epub 2006 May 15. — View Citation
* Note: There are 18 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Proportion of individuals progressing to meet RDS criteria as defined by the American- European ARDS consensus conference and as used by ARDSnet. | Day 28 | No | |
Secondary | Ventilator-free days to Day 28 | Day 28 | No | |
Secondary | 28 day all-cause mortality | Day 28 | No | |
Secondary | Proportion of subjects progressing to acute lung injury (who do not meet the definition at randomization) | Day 28 | No | |
Secondary | Worst PaO2/FiO2 ratio recorded following enrollment | Day 3 and 28 | No | |
Secondary | Change in PaO2/FiO2 ratio between Day 0 to Day 3 | Day 0 and Day 3 | No | |
Secondary | Change from baseline in number of non-lung organ failures using the Multi-Organ Dysfunction (MOD) score and Sepsis Organ Failure Assessment (SOFA) score | Day 0, Day 28 | No | |
Secondary | Proportion of subjects surviving to hospital discharge | Hospital Discharge Day | No | |
Secondary | Vasopressor-free days | Day 28 | No | |
Secondary | Reversal of shock if present at randomization. | Day 28 | No |
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