Ignite Creation Date:
2024-05-05 @ 5:26 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00457951
Status:
TERMINATED
Last Update Posted:
2021-12-02
First Post:
2007-04-06
Brief Title:
A Study Designed to Evaluate ODSH in Subjects With Exacerbations of COPD
Sponsor:
Chimerix
Organization:
Chimerix
Study Overview
Official Title:
An Open-Label Phase Followed by a Randomized Double-Blind Placebo-Controlled Phase in a Study Designed to Evaluate Intravenous 2-O 3-O Desulfated Heparin ODSH in Subjects With Exacerbations of Chronic Obstructive Pulmonary Disease
Status:
TERMINATED
Status Verified Date:
2016-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Interim analysis safety without efficacy ODSH in patients with acute COPD
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
COPD
Brief Summary:
The purpose of this study is to determine whether ODSH when added to conventional treatment is more effective in treating COPD exacerbations than conventional therapy alone
Detailed Description:
The management of acute exacerbations of COPD today is qualitatively the same as it was 40 years ago bronchodilators corticosteroids and antibiotics Because of the prominent pathophysiological role of neutrophils in exacerbations of COPD neutrophils and their toxic oxidants and proteases represent therapeutic targets which are currently unchallenged in the treatment of this aspect of the disease Ideally to disrupt neutrophilic airway inflammation one would both block neutrophilic influx from the vascular space into the airway as well as neutralize or inactivate prominent neutrophilic toxins such as the proteases HLE and cathepsin G
Heparin is a sulfated mucopolysaccharide that slows blood clot formation by inhibiting the reactions that lead to formation of fibrin clots Physicians use heparin to prevent blood clot formation during open-heart surgery bypass surgery and dialysis Heparin also prevents previously formed clots from becoming larger and causing more serious problems Heparin has other biological properties most notably anti-inflammatory activity At doses required to be therapeutically beneficial as an anti-inflammatory heparin can cause severe potentially life-threatening hemorrhage ParinGenix has chemically modified heparin to retain the anti-inflammatory activity while reducing anti-coagulant properties
Heparin has long been known to be a potent inhibitor both in vitro and in vivo of the cationic neutrophil proteases HLE and cathepsin G However heparin also has numerous other important anti-inflammatory effects P-selectin is the primary endothelial attachment molecule mediating neutrophil rolling along the vessel wall At concentrations close to those achieved in plasma near the high range of therapeutic anticoagulation heparin inhibits P-selectin and P-selectin mediated interaction of leukocytes with endothelium Heparin also blocks the leukocyte integrin Mac-1 CD11bCD18 and Mac-1-dependent leukocyte adherence to endothelial ICAM These combined effects on rolling integrin-dependent attachment and perhaps other aspects of cellular passage through the basement membrane prevent neutrophil accumulation in areas of inflammation As an example when given in much higher concentrations than those appropriate for therapeutic anticoagulation heparin efficiently blocks neutrophilic influx into ischemic reperfused myocardium and brain reducing the size of both myocardial infarction and ischemic stroke Thus heparin and heparin analogues may have the potential to also reduce inflammatory influx of neutrophils into the airway during exacerbations of COPD
All subjects will receive standard of care treatment including corticosteroids beta-2 agonists and antibiotics as well as ODSH or placebo
Heparin is a sulfated mucopolysaccharide that slows blood clot formation by inhibiting the reactions that lead to formation of fibrin clots Physicians use heparin to prevent blood clot formation during open-heart surgery bypass surgery and dialysis Heparin also prevents previously formed clots from becoming larger and causing more serious problems Heparin has other biological properties most notably anti-inflammatory activity At doses required to be therapeutically beneficial as an anti-inflammatory heparin can cause severe potentially life-threatening hemorrhage ParinGenix has chemically modified heparin to retain the anti-inflammatory activity while reducing anti-coagulant properties
Heparin has long been known to be a potent inhibitor both in vitro and in vivo of the cationic neutrophil proteases HLE and cathepsin G However heparin also has numerous other important anti-inflammatory effects P-selectin is the primary endothelial attachment molecule mediating neutrophil rolling along the vessel wall At concentrations close to those achieved in plasma near the high range of therapeutic anticoagulation heparin inhibits P-selectin and P-selectin mediated interaction of leukocytes with endothelium Heparin also blocks the leukocyte integrin Mac-1 CD11bCD18 and Mac-1-dependent leukocyte adherence to endothelial ICAM These combined effects on rolling integrin-dependent attachment and perhaps other aspects of cellular passage through the basement membrane prevent neutrophil accumulation in areas of inflammation As an example when given in much higher concentrations than those appropriate for therapeutic anticoagulation heparin efficiently blocks neutrophilic influx into ischemic reperfused myocardium and brain reducing the size of both myocardial infarction and ischemic stroke Thus heparin and heparin analogues may have the potential to also reduce inflammatory influx of neutrophils into the airway during exacerbations of COPD
All subjects will receive standard of care treatment including corticosteroids beta-2 agonists and antibiotics as well as ODSH or placebo
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None