A Study Designed to Evaluate ODSH in Subjects With Exacerbations of COPD

Chronic Obstructive Pulmonary Disease Clinical Trial

— COPD  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00457951
• Other study ID #: PGX-ODSH-2006
• Status: Terminated
• Phase: Phase 2
• Start date: April 2007
• Est. completion date: October 2009

Study information

• Verified date: October 2016
• Source: Chimerix
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 158
• Est. completion date: October 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. 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;

2. Normal prothrombin time and activated partial thromboplastin time; Platelet count; hemoglobin and hematocrit

Exclusion Criteria:

1. 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

2. Certain medications such as:

• Plavix®
• Warfarin
• Heparin therapy
• Certain antibiotics

3. Exacerbations that are too severe (requiring intubation and mechanical ventilation)

4. Women of child-bearing potential, pregnancy or breast-feeding

5. Unable or unwilling to provide informed consent and follow study procedures.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Open-Label
ODSH administered open-label
• Placebo Comparator: Placebo-Control Arm 0.9% Sodium Chloride
Placebo-Control Arm: Bolus infusion followed by a 96 hour continuous infusion of 0.9%Sodium Chloride
• ODSH
Randomized, Blinded, ODSH Arm

Locations

Country	Name	City	State
Belgium	University Hospital Gasthuisberg	Leuven
Belgium	CHU Liege Domain Universitaire du Sart Tilman	Liege
Belgium	Cliniques Universiaries U.C.L. de Mont-Gondinne	Yvior
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	QE II Health Sciences Centre	Halifax	Nova Scotia
Canada	Kelowna General Hospital	Kelowna	British Columbia
Canada	Credit Valley Hospital,	Mississauga	Ontario
Canada	The Ottawa Hospital, Civic Campus	Ottawa	Ontario
Canada	Laval Hospital	Quebec City	Quebec
Canada	University of Toronto	Toronto	Ontario
Canada	Vancouver Coastal Health	Vancouver	British Columbia
Canada	St. Boniface General Hospital	Winnipeg	Manitoba
Germany	Klinik Schillerhohe	Gerlingen
Germany	Pneumologisches Forschungsinstitut GmbH	Grosshansdorf
Germany	Medizinsche Hochschule	Hannover
Germany	Uniklinikum Mainz	Mainz
Germany	Klinikum der LMU Innenstadt	Munchen
Poland	Wojewodzki Szpital Specjalistyczny im. Najswietszej Marii Panny	Czestochowa
Poland	Samodzielny Publiczny Szpital Kliniczny SUM w Katowicach	Katowice
Poland	Krakowski Szpital Specjalistyczny im. Jana Pawla II	Krakow
Poland	Samodzielny Publiczny ZOZ, Uniwersytecki Szpital Liniczny nr 1 im Norberta Barlickiego	Lodz
Poland	Samodzielny Publiczny Szpital Klinczny nr 4 W Lublinie	Lublin
Poland	Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego, Samodzielny Publiczny Zespol Opieki Zdrowotnej	Lublin
Poland	Zespol Opieki Zdrowotnej w Olawie	Olawa
Poland	Wieklopolskie Centrum Chorob Pluc i Gruzlicy	Poznan
Poland	I Klinika Chorob Plus, Instyut Gruzlicy i Chorob Pluc	Warszawa
Poland	Miedzyleski Szpital Specjalistyczny w Warszawie	Warszawa
Poland	Akademicki Szpital Kliniczny im. Jana Mikulicza-Radeckiego	Wroclaw
United States	Western Washington Medical Group	Everett	Washington
United States	Methodist Hospital	Houston	Texas
United States	Michael E. DeBakey VA Medical Center	Houston	Texas
United States	Wellstar Kennestone Hospital	Marietta	Georgia
United States	Pulmonary Consultants & Primary Care	Orange	California
United States	Temple University of the Commonwealth of Higher Education	Philadelphia	Pennsylvania
United States	The Oregon Clinic	Portland	Oregon
United States	Washington Universtiy School of Medicine	Saint Louis	Missouri
United States	Louisiana State University Health Sciences Center in Shreveport	Shreveport	Louisiana
United States	University of Texas Health Care Center at Tyler	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Chimerix

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment Failure	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.	Time to hospital discharge and 21 days post-treatment, up to 31 days