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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00457951
Recruitment Status : Terminated (Interim analysis: safety without efficacy ODSH in patients with acute COPD.)
First Posted : April 9, 2007
Results First Posted : December 16, 2016
Last Update Posted : December 16, 2016
Information provided by (Responsible Party):
Cantex Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Drug: Open-Label Drug: Placebo Comparator: Placebo-Control Arm 0.9% Sodium Chloride Drug: ODSH Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 158 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Study Start Date : April 2007
Actual Primary Completion Date : August 2009
Actual Study Completion Date : October 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: COPD
U.S. FDA Resources

Arm Intervention/treatment
Experimental: 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.
Drug: Open-Label
ODSH administered open-label
Other Name: PGX-100
Placebo Comparator: 0.9% Sodium Chloride
Placebo Comparator: Placebo-Control Arm 0.9% Sodium Chloride Solution bolus; dose of 0.375mg/kg/hr over 96 hours.
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
Other Name: 0.9% Sodium Chloride Solution Placebo-Control Arm
Active Comparator: 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.
Drug: ODSH
Randomized, Blinded, ODSH Arm
Other Name: PGX-100

Primary Outcome Measures :
  1. Incidence of Treatment Failure [ Time Frame: 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00457951

  Show 38 Study Locations
Sponsors and Collaborators
Cantex Pharmaceuticals
Principal Investigator: Marc Decramer, MD Université Hopistal Gasthuisberg
Study Director: Pedro Quintana, MD Cantex Pharmaceuticals
Principal Investigator: Tobias Welte, MD Hannover Medical School

Responsible Party: Cantex Pharmaceuticals Identifier: NCT00457951     History of Changes
Other Study ID Numbers: PGX-ODSH-2006
First Posted: April 9, 2007    Key Record Dates
Results First Posted: December 16, 2016
Last Update Posted: December 16, 2016
Last Verified: October 2016

Keywords provided by Cantex Pharmaceuticals:
Chronic Obstructive Pulmonary Disease
Exacerbations of COPD

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action