A Study Designed to Evaluate ODSH in Subjects With Exacerbations of COPD
- Conditions
- Chronic Obstructive Pulmonary Disease
- Interventions
- Drug: Open-Label
- Registration Number
- NCT00457951
- Lead Sponsor
- Chimerix
- 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 (CD11b/CD18) 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 158
- Male and female patients (40 years of age or older) with an established diagnosis of COPD based upon medical history who are being admitted to the hospital to treat an exacerbation of COPD;
- Normal prothrombin time and activated partial thromboplastin time; Platelet count; hemoglobin and hematocrit
-
Certain diseases such as:
- asthma;
- left heart failure or pulmonary embolism;
- lung cancer;
- pneumonia
- liver or kidney disease
- blood clotting disorder
- Positive HIV or hepatitis tests
- GI bleeding, physical trauma with bleeding, any disease with bleeding within 60 days of study entry
-
Certain medications such as:
- Plavix®
- Warfarin
- Heparin therapy
- Certain antibiotics
-
Exacerbations that are too severe (requiring intubation and mechanical ventilation)
-
Women of child-bearing potential, pregnancy or breast-feeding
-
Unable or unwilling to provide informed consent and follow study procedures.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Open Label Open-Label Initial six subjects treated with ODSH open-label to confirm safety in subjects with an acute exacerbation of COPD; six additional patients will be enrolled following safety review. Randomized, Blinded, ODSH Arm ODSH Subjects will receive standard of care treatment. ODSH is administered in bolus doses estimated to inhibit inflammatory mediators randomized 1:1 to ODSH 8mg/kg or placebo. The continuous infusion dose will be 0.375 mg/kg/hr over 96 hours.
- Primary Outcome Measures
Name Time Method Incidence of Treatment Failure Time to hospital discharge and 21 days post-treatment, up to 31 days The primary outcome of the study is "Treatment Failure" as defined by Failure to discharge from hospital based on GOLD (Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease) criteria or relapse after DC from hospital.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (38)
University of Toronto
🇨🇦Toronto, Ontario, Canada
Louisiana State University Health Sciences Center in Shreveport
🇺🇸Shreveport, Louisiana, United States
University Hospital Gasthuisberg
🇧🇪Leuven, Belgium
Kelowna General Hospital
🇨🇦Kelowna, British Columbia, Canada
Cliniques Universiaries U.C.L. de Mont-Gondinne
🇧🇪Yvior, Belgium
Vancouver Coastal Health
🇨🇦Vancouver, British Columbia, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Akademicki Szpital Kliniczny im. Jana Mikulicza-Radeckiego
🇵🇱Wroclaw, Poland
QE II Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
Wojewodzki Szpital Specjalistyczny im. Najswietszej Marii Panny
🇵🇱Czestochowa, Poland
I Klinika Chorob Plus, Instyut Gruzlicy i Chorob Pluc
🇵🇱Warszawa, Poland
Samodzielny Publiczny ZOZ, Uniwersytecki Szpital Liniczny nr 1 im Norberta Barlickiego
🇵🇱Lodz, Poland
St. Boniface General Hospital
🇨🇦Winnipeg, Manitoba, Canada
Wellstar Kennestone Hospital
🇺🇸Marietta, Georgia, United States
Pulmonary Consultants & Primary Care
🇺🇸Orange, California, United States
Washington Universtiy School of Medicine
🇺🇸Saint Louis, Missouri, United States
The Oregon Clinic
🇺🇸Portland, Oregon, United States
Temple University of the Commonwealth of Higher Education
🇺🇸Philadelphia, Pennsylvania, United States
Michael E. DeBakey VA Medical Center
🇺🇸Houston, Texas, United States
Methodist Hospital
🇺🇸Houston, Texas, United States
University of Texas Health Care Center at Tyler
🇺🇸Tyler, Texas, United States
CHU Liege Domain Universitaire du Sart Tilman
🇧🇪Liege, Belgium
Western Washington Medical Group
🇺🇸Everett, Washington, United States
Uniklinikum Mainz
🇩🇪Mainz, Germany
The Ottawa Hospital, Civic Campus
🇨🇦Ottawa, Ontario, Canada
Credit Valley Hospital,
🇨🇦Mississauga, Ontario, Canada
Pneumologisches Forschungsinstitut GmbH
🇩🇪Grosshansdorf, Germany
Laval Hospital
🇨🇦Quebec City, Quebec, Canada
Klinik Schillerhohe
🇩🇪Gerlingen, Germany
Medizinsche Hochschule
🇩🇪Hannover, Germany
Samodzielny Publiczny Szpital Kliniczny SUM w Katowicach
🇵🇱Katowice, Poland
Klinikum der LMU Innenstadt
🇩🇪Munchen, Germany
Krakowski Szpital Specjalistyczny im. Jana Pawla II
🇵🇱Krakow, Poland
Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego, Samodzielny Publiczny Zespol Opieki Zdrowotnej
🇵🇱Lublin, Poland
Samodzielny Publiczny Szpital Klinczny nr 4 W Lublinie
🇵🇱Lublin, Poland
Zespol Opieki Zdrowotnej w Olawie
🇵🇱Olawa, Poland
Wieklopolskie Centrum Chorob Pluc i Gruzlicy
🇵🇱Poznan, Poland
Miedzyleski Szpital Specjalistyczny w Warszawie
🇵🇱Warszawa, Poland