A trial examining the effects of alteplase in patients with severe respiratory failure.

A randomized phase II pilot - trial, examining the safety, pharmacokinetics, pharmacodynamics, and clinical efficacy of escalating doses of alteplase in patients with acute lung injury / acute respiratory distress syndrome / severe pneumonia - TPA-ALI

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2010-024377-40-AT

Enrollment

Unknown

Registered

2011-05-23

Start date

2011-06-29

Completion date

Unknown

Last updated

2017-05-22

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

Conditions

acute lung injury, acute respiratory distress syndrom, severe pneumonia

Interventions

Trade Name: Actilyse Product Name: actilyse Pharmaceutical Form: Powder for solution for injection/infusion INN or Proposed INN: ALTEPLASE CAS Number: 105857-23-6 Concentration unit: mg milligram(s) C

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Subjects fulfilling the criteria for ALI/ARDS/severe pneumonia and need for a ventilator Negative urine pregnancy test acute stage ALI/ARDS/severe pneumonia Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30

Exclusion criteria

Exclusion criteria: • Known or suspected allergy to trial product or related products • History of heparin induced thrombocytopenia type II • Treatment with an investigational drug within three weeks prior to this trial • Pregnancy (pregnancy will be ruled out in women of childbearing age by urine test) • Severe bleeding disorder (acute or within last 6 months) • Known bleeding diathesis • Patients on oral anticoagulant therapy at randomization • Overt or recent severe or life-threatening bleeding • Present or known or suspected intracranial bleeding • Suspicion of subarachnoid hemorrhage or history of aneurismal subarachnoid hemorrhage • History of intracranial neoplasm, aneurysm, intracranial or intraspinal surgery • Recent (less than 10 days) traumatic CPR, obstetric delivery; • Severe uncontrolled arterial hypertension • Bacterial endocarditis, pericarditis • Acute pancreatitis • Evidence of ulcera disease gastrointestinal tract within 3 months, esophageal varices, arterial aneurysm, arteriovenous malformations; • Neoplasm with high bleeding risk • Severe liver disease including liver failure, cirrhosis, portal hypertension, acute hepatitis; • Major trauma or major surgery within 3 months • Patients at the age of over 80 and under 18 years • Hemorrhagic stroke or history of stroke of unknown origin; • Known ischemic stroke or transient ischemic attack in the last 6 months • Patients on drotrecogin alpha therapy • Aspirin therapy >650mg q day

Design outcomes

Primary

Measure	Time frame
Main Objective: To investigate safety, pharmacokinetics, pharmacodynamics, and clinical efficacy of escalating doses of alteplase in patients with acute lung injury / acute respiratory distress syndrome / severe pneumonia;Secondary Objective: Disease-related-biomarkers, clinical assessment, mortality, safety parameters, PK and PD parameters;Primary end point(s): - PaO2 (partial arterial oxygen pressure)/FiO2 (fraction of inspired oxygen) ratio before and at the end of infusion, at 4, 6, 24, 30, 48, 54, and 72h after the start of the infusion (AUC);Timepoint(s) of evaluation of this end point: Before treatment 1,2,4,6,24,30,48,54,72 hours after start of treatment	—

Measure

Time frame

Main Objective: To investigate safety, pharmacokinetics, pharmacodynamics, and clinical efficacy of escalating doses of alteplase in patients with acute lung injury / acute respiratory distress syndrome / severe pneumonia;Secondary Objective: Disease-related-biomarkers, clinical assessment, mortality, safety parameters, PK and PD parameters;Primary end point(s): - PaO2 (partial arterial oxygen pressure)/FiO2 (fraction of inspired oxygen) ratio before and at the end of infusion, at 4, 6, 24, 30, 48, 54, and 72h after the start of the infusion (AUC);Timepoint(s) of evaluation of this end point: Before treatment 1,2,4,6,24,30,48,54,72 hours after start of treatment

—

Secondary

Measure	Time frame
Secondary end point(s): Secondary A variety of parameters will be assessed to characterize the pharmacodynamics of tPA infusion: - Prothrombin time (PT) or Normotest® - Activated partial thromboplastin time (aPTT) - Fibrinogen - D-Dimer - Rotation thrombelastography (ROTEM®) - t-PA (antigen and activity) in plasma (ELISA) - plasminogen activator inhibitor-1 (PAI-1) - plasmin antiplasmin complexes (PAP) - a2 - antiplasmin - plasminogen Disease-related-biomarkers: SP-D, sICAM, IL-8, PC, TM, vWF, TNFR-1 Evaluation of safety Bleedings, clinical assessment including APACHE and SOFA scores over time, frequent complete blood counts, laboratory parameters and adverse events. 28 and 90 days mortality, incidence of organ failure at the ICU, duration of mechanical ventilation and length of stay at the ICU and in hospital, number of days without failure of non-pulmonary organs within the first 28 days. ;Timepoint(s) of evaluation of this end point: before treatment, 1 2 4 6 24 30 48 54 72 hours, 8 days,28 days, 90 days after start of treatment (depending on each endpoint)	—

Measure

Time frame

Secondary end point(s): Secondary A variety of parameters will be assessed to characterize the pharmacodynamics of tPA infusion: - Prothrombin time (PT) or Normotest® - Activated partial thromboplastin time (aPTT) - Fibrinogen - D-Dimer - Rotation thrombelastography (ROTEM®) - t-PA (antigen and activity) in plasma (ELISA) - plasminogen activator inhibitor-1 (PAI-1) - plasmin antiplasmin complexes (PAP) - a2 - antiplasmin - plasminogen Disease-related-biomarkers: SP-D, sICAM, IL-8, PC, TM, vWF, TNFR-1 Evaluation of safety Bleedings, clinical assessment including APACHE and SOFA scores over time, frequent complete blood counts, laboratory parameters and adverse events. 28 and 90 days mortality, incidence of organ failure at the ICU, duration of mechanical ventilation and length of stay at the ICU and in hospital, number of days without failure of non-pulmonary organs within the first 28 days. ;Timepoint(s) of evaluation of this end point: before treatment, 1 2 4 6 24 30 48 54 72 hours, 8 days,28 days, 90 days after start of treatment (depending on each endpoint)

—

Countries

Austria

Contacts

Public ContactBernd Jilma

UniKlinik für Klinische Pharmakologie

bernd.jilma@meduniwien.ac.at+431404002981

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026