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Sponsors and Collaborators: |
Medical Center of Central Georgia Genentech |
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Information provided by: | Medical Center of Central Georgia |
ClinicalTrials.gov Identifier: | NCT00431379 |
The pathogenesis of ARDS appears to be from damage to the alveolar-capillary barrier, which is composed of the microvascular endothelium and the alveolar epithelium. This damage may occur from direct or indirect lung injury. The mechanism of injury to the alveolar capillary barrier appears to be through neutrophil-mediated injury, pro-inflammatory cytokines, ventilator-induced lung injury with alveolar over distention and abnormalities of the coagulation system. This results in blood clot formation in the microcirculation of the lung. Thrombolytics can dissolve blood clots and result in increased blood flow to the organs. This treatment may benefit ARDS patients, thus the purpose of this study.
Hardaway, et al.studied the effects of thrombolytics on ARDS in pigs. The experimental group showed improved oxygenation and survival as compared to controls. There was no bleeding complications noted with this therapy. Dr. Hardaway followed this animal study with a phase I clinical trial involving 20 patients with ARDS. The patients were treated with IV streptokinase or urokinase. Nineteen of the 20 patients showed an increase in PA02 after thrombolytic therapy. There were no significant bleeding complications in patients that were critically ill on ventilators.
We propose an additional phase I pilot study to evaluate the effectiveness and safety of Tenecteplase for the treatment of ARDS. Unlike the other fibrinolytics studied in this disease state, Tenecteplase, is more fibrin specific and has increased resistance to plasminogen activator inhibitor (PAI-I) at greater levels than other available fibrinolytics. We have chosen an experimental dose escalation trial design of tenecteplase that has demonstrated initial safety trends in a Phase I acute ischemic stroke trial. The initial dose is 0.1 mg/kg IV and will increase to 0.2 mg/kg, 0.3 mg/kg, with a final cohort of patients receiving 0.4 mg/kg. Drug administration will be a single dose bolus in each cohort. Advancement of dose will occur if safety is not in question in the previous cohort. We hope this will provide an acceptable benefit risk ratio as the mortality of ARDS is approximately 30 - 60%. All patients will be closely monitored for any change in clotting parameters and signs of bleeding. Tenecteplase will be administered via a peripheral IV as described in the package insert.
Condition | Intervention | Phase |
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Acute Respiratory Distress Syndrome |
Drug: Tenecteplase |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety Study |
Official Title: | Treatment of Acute Respiratory Distress Syndrome With Tenecteplase: A Dose Escalation Pilot Study: Phase I |
Estimated Enrollment: | 20 |
Study Start Date: | February 2007 |
Estimated Study Completion Date: | February 2009 |
Estimated Primary Completion Date: | November 2008 (Final data collection date for primary outcome measure) |
Ages Eligible for Study: | 18 Years to 75 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Other considerations
Exclusion Criteria:
Contact: Dennis W Ashley, MD, FACS | 478-633-1199 | ashley.dennis@mccg.org |
Contact: Debra M Kitchens, RN,CEN | 478-633-1584 | kitchens.debra@mccg.org |
United States, Georgia | |
Medical Center of Central GA | Recruiting |
Macon, Georgia, United States, 31201 | |
Contact: Debra M Kitchens, RN, CEN 478-633-1584 kitchens.debra@mccg.org | |
Principal Investigator: Dennis W Ashley, MD, FACS |
Principal Investigator: | Dennis W. Ashley, MD, FACS | Medical Center of Central GA |
Study Chair: | Debra M Kitchens, RN, CEN | Medical Center of Central Georgia |
Responsible Party: | Genentech ( Pat Reilly, RN, MSN ) |
Study ID Numbers: | H0605329 |
Study First Received: | February 2, 2007 |
Last Updated: | June 19, 2008 |
ClinicalTrials.gov Identifier: | NCT00431379 |
Health Authority: | United States: Food and Drug Administration |
Respiratory Tract Diseases Lung Diseases Respiration Disorders |
Respiratory Distress Syndrome, Adult Tenecteplase Acute respiratory distress syndrome |
Fibrin Modulating Agents Pathologic Processes Disease Molecular Mechanisms of Pharmacological Action Therapeutic Uses |
Syndrome Hematologic Agents Fibrinolytic Agents Cardiovascular Agents Pharmacologic Actions |