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

NCT ID: NCT00457951

Last Updated: 2021-12-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 158 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2009-10-31

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Chronic Obstructive Pulmonary Disease; COPD; Heparin; ODSH; Exacerbations of COPD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Open-Label

Intervention Type: DRUG

ODSH administered open-label

0.9% Sodium Chloride

Placebo Comparator: Placebo-Control Arm 0.9% Sodium Chloride Solution bolus; dose of 0.375mg/kg/hr over 96 hours.

Group Type: PLACEBO_COMPARATOR

Placebo Comparator: Placebo-Control Arm 0.9% Sodium Chloride

Intervention Type: DRUG

Placebo-Control Arm: Bolus infusion followed by a 96 hour continuous infusion of 0.9%Sodium Chloride

Randomized, Blinded, ODSH Arm

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.

Group Type: ACTIVE_COMPARATOR

ODSH

Intervention Type: DRUG

Randomized, Blinded, ODSH Arm

Interventions

Open-Label

ODSH administered open-label

Intervention Type: DRUG

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

Intervention Type: DRUG

ODSH

Randomized, Blinded, ODSH Arm

Intervention Type: DRUG

Other Intervention Names

PGX-100; 0.9% Sodium Chloride Solution Placebo-Control Arm; PGX-100

Eligibility Criteria

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tobias Welte, MD

Role: PRINCIPAL_INVESTIGATOR

Hannover Medical School

Locations

Pulmonary Consultants & Primary Care

Orange, California, United States

Wellstar Kennestone Hospital

Marietta, Georgia, United States

Louisiana State University Health Sciences Center in Shreveport

Shreveport, Louisiana, United States

Washington Universtiy School of Medicine

St Louis, Missouri, United States

The Oregon Clinic

Portland, Oregon, United States

Temple University of the Commonwealth of Higher Education

Philadelphia, Pennsylvania, United States

Methodist Hospital

Houston, Texas, United States

Michael E. DeBakey VA Medical Center

Houston, Texas, United States

University of Texas Health Care Center at Tyler

Tyler, Texas, United States

Western Washington Medical Group

Everett, Washington, United States

University Hospital Gasthuisberg

Leuven, , Belgium

CHU Liege Domain Universitaire du Sart Tilman

Liège, , Belgium

Cliniques Universiaries U.C.L. de Mont-Gondinne

Yvior, , Belgium

University of Alberta Hospital

Edmonton, Alberta, Canada

Kelowna General Hospital

Kelowna, British Columbia, Canada

Vancouver Coastal Health

Vancouver, British Columbia, Canada

St. Boniface General Hospital

Winnipeg, Manitoba, Canada

QE II Health Sciences Centre

Halifax, Nova Scotia, Canada

Credit Valley Hospital,

Mississauga, Ontario, Canada

The Ottawa Hospital, Civic Campus

Ottawa, Ontario, Canada

University of Toronto

Toronto, Ontario, Canada

Laval Hospital

Québec, Quebec, Canada

Klinik Schillerhohe

Gerlingen, , Germany

Pneumologisches Forschungsinstitut GmbH

Großhansdorf, , Germany

Medizinsche Hochschule

Hanover, , Germany

Uniklinikum Mainz

Mainz, , Germany

Klinikum der LMU Innenstadt

München, , Germany

Wojewodzki Szpital Specjalistyczny im. Najswietszej Marii Panny

Częstochowa, , 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

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

Oława, , Poland

Wieklopolskie Centrum Chorob Pluc i Gruzlicy

Poznan, , Poland

I Klinika Chorob Plus, Instyut Gruzlicy i Chorob Pluc

Warsaw, , Poland

Miedzyleski Szpital Specjalistyczny w Warszawie

Warsaw, , Poland

Akademicki Szpital Kliniczny im. Jana Mikulicza-Radeckiego

Wroclaw, , Poland

Countries

United States; Belgium; Canada; Germany; Poland

Other Identifiers

PGX-ODSH-2006

Identifier Type: -

Identifier Source: org_study_id