Fibrinolytic treatment of acute respiratory failure due to inflammatory lung injury

Fibrinolytic treatment of acute respiratory failure due to inflammatory lung injury to assess improvement in alveolar dead space and right ventricular function

Status

Not yet recruiting

Phases

Phase 1

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12610000950066

Enrollment

Registered

2010-11-05

Start date

2010-12-12

Completion date

Unknown

Last updated

2020-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

Inflammatory insults including pneumonia, sepsis, aspiration, trauma, prolonged hypotension, cardiac surgery and pancreatitis can cause lung damage. One mechanism by which inflammation mediates lung injury is through deposition of fibrin in the pulmonary microcirculation. This study will investigate if limiting fibrin deposition through administration of tissue plasminogen activator reduces lung damage.

Interventions

Administration of tissue plasminogen activator (t-PA) on one occasion. Dose escalation study The first 4 patients will receive 1. 10 mg bolus and 10 mg over 30 min. The second 4 patients will receive 2. 10 mg bolus and 20 mg over 30 min. The final 4 patients will receive 3. 10 mg bolus and 40 mg over 30 min.

Study design

Allocation

Non-randomised trial

Intervention model

Single group

Primary purpose

Treatment

Masking

Open (masking not used)

Eligibility

Sex/Gender

All

Age

15 Years to No maximum

Healthy volunteers

Inclusion criteria

Patients with acute respiratory failure due to an acute inflammatory insult. Requiring positive pressure ventilation via an endo-tracheal tube. Impaired oxygenation - arterial partial pressure of oxygen to inspire fraction of oxygen ratio (P/F) <300 mmHg. At least one quadrant of pulmonary infiltrate present on CXR. Enrolled within 24 hrs of developing all of these criteria.

Exclusion criteria

Known hypersensitivity to alteplase (t-PA) Aspirin in the last week Any therapeutic anti-coagulant therapy Significant bleeding disorder within the past six months Any history of brain or spinal injury including trauma, stroke, transient ischaemic attack, neoplasm, surgery, infection, aneurysm or intracranial bleed. Uncontrolled hypertension, systolic blood pressure (BP) >185 mmHg or diastolic BP >110 mmHg. Recent (within ten days) prolonged or traumatic cardiopulmonary resuscitation (> 2 minutes), obstetric delivery, organ biopsy, puncture of non-compressible blood vessel (e.g. subclavian vein), major surgery or significant trauma. Documented ulcerative gastrointestinal disease during the last three months. Arterial aneurysms, arterial/venous malformations. Neoplasm with increased bleeding risk. Bacterial endocarditis, pericarditis. Acute pancreatitis. Severe hepatic disease/ dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) or active hepatitis. Age <18 or > 75 Pulmonary haemorrhage in previous 12 months Major surgery planned over the next 2 days Diabetic haemorrhagic retinopathy or other haemorrhagic ophthalmic conditions. Unlikely to survive 24 hours Platelet count below 80,000/mm3

Outcome results