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

This study has been terminated.
(Interim analysis results showed evidence of safety without efficacy of ODSH in patients with acute COPD.)
Sponsor:
Information provided by (Responsible Party):
Cantex Pharmaceticals
ClinicalTrials.gov Identifier:
NCT00457951
First received: April 6, 2007
Last updated: December 13, 2012
Last verified: December 2012
  Purpose

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 Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: Normal Saline infusion
Drug: ODSH
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Cantex Pharmaceticals:

Primary Outcome Measures:
  • Treatment Failure [ Time Frame: Time to hospital discharge and 21 days post-treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • pulmonary function tests and arterial blood gas [ Time Frame: 21 days post-treatment ] [ Designated as safety issue: No ]
  • CRP [ Time Frame: 21 days post-treatment ] [ Designated as safety issue: No ]
  • Changes in Borg CR10 scale [ Time Frame: 21 days post-treatment ] [ Designated as safety issue: No ]
  • 6 minute walk test [ Time Frame: 21 days post-treatment ] [ Designated as safety issue: No ]
  • BODE Index [ Time Frame: 21 days post-treatment ] [ Designated as safety issue: No ]
  • Need for intubation or mechanical ventilation [ Time Frame: During initial hospitalization ] [ Designated as safety issue: Yes ]
  • Amount of rescue beta-agonist use [ Time Frame: During initial hospitalization ] [ Designated as safety issue: No ]
  • Oxygen requirements [ Time Frame: During initial hospitalization ] [ Designated as safety issue: No ]
  • Length of hospitalization or ICU stay [ Time Frame: During initial hospitalization ] [ Designated as safety issue: Yes ]
  • Time to new exacerbation [ Time Frame: 90 days post-treatment ] [ Designated as safety issue: No ]
  • Incidence of exacerbations [ Time Frame: 90 days post-treatment ] [ Designated as safety issue: Yes ]
  • Hospitalization for COPD exacerbation [ Time Frame: 60 days post-treatment ] [ Designated as safety issue: Yes ]
  • Hospitalization for COPD exacerbation [ Time Frame: 90 days post-treatment ] [ Designated as safety issue: Yes ]
  • Death [ Time Frame: 30, 60 or 90 days post-treatment ] [ Designated as safety issue: Yes ]

Enrollment: 150
Study Start Date: April 2007
Study Completion Date: October 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
ODSH infusion
Drug: ODSH
Bolus infusion followed by a 4 day continuous infusion of ODSH
Other Name: PGX-100
Placebo Comparator: 2
Normal Saline infusion
Drug: Normal Saline infusion
Bolus infusion followed by a 4 day continuous infusion of placebo

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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00457951

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

No publications provided

Responsible Party: Cantex Pharmaceticals
ClinicalTrials.gov Identifier: NCT00457951     History of Changes
Other Study ID Numbers: PGX-ODSH-2006
Study First Received: April 6, 2007
Last Updated: December 13, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices
Belgium: Federal Agency for Medicines and Health Products, FAMHP

Keywords provided by Cantex Pharmaceticals:
Chronic Obstructive Pulmonary Disease
COPD
Heparin
ODSH
Exacerbations of COPD

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 22, 2014