Trial · NCT04640194
A Study to Test Whether Different Doses of Alteplase Help People With Severe Breathing Problems Because of COVID-19
NCT04640194, Phase 2, Phase 3, Completed, Boehringer Ingelheim; results first posted 2024-03-07
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Study to Test Whether Different Doses of Alteplase Help People With Severe Breathing Problems Because of COVID-19. Trials, record NCT04640194. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04640194
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Study to Test Whether Different Doses of Alteplase Help People With Severe Breathing Problems Because of COVID-19
- NCT number
- NCT04640194
- Status
- Completed
- Phases
- Phase 2, Phase 3
- Enrollment
- 104 participants, actual
- Lead sponsor
- Boehringer Ingelheim
- Conditions
- Acute Respiratory Distress Syndrome
- Interventions
- Standard of care, Alteplase low dose, Alteplase high dose
- First posted
- 2020-11-23
- Last updated
- 2024-03-20
- Other registries' IDs
- eudract:2020-002913-16
- Results first posted
- 2024-03-07
- Limitations and caveats
Results for the invasive mechanical ventilation (IMV) patients were only analyzed descriptively due to insufficient enrolled patients. For the All-Cause Mortality endpoint, the non-invasive mechanical ventilation (NIV) arm did not have enough events to perform the adjusted statistical model, instead the unadjusted model is presented for this endpoint.
Source ClinicalTrials.gov
Registered outcomes10
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Time to Clinical Improvement or Hospital Discharge up to Day 28 | Up to 28 days. | From randomisation to either an improvement of 2 points on the 11-point World Health Organization (WHO) Clinical Progression Scale (from 0 to 10, a low score indicates a better outcome) or discharge from the hospital, whichever comes first. Full scale: 0=Uninfected; no viral RNA detected 1. Asymptomatic; viral RNA detected 2. Symptomatic; independent 3. Symptomatic; assistance needed 4. Hospitalised; no oxygen therapy 5. Hospitalised; oxygen by mask or nasal prongs 6. Hospitalised; oxygen by NIV or high flow 7. Intubation and mechanical ventilation, PaO2/FiO2=150 or SpO2/FiO2=200 8. Mechanical ventilation PaO2/FiO2\<150 (SpO2/FiO2\<200) or vasopressors 9. Mechanical ventilation PaO2/FiO2\<150 and vasopressors, dialysis, or ECMO 10. Dead Patients that have not met the endpoint were censored at Day 28 if they died prior to Day 28. Patients receiving bail out therapy without having first met the endpoint, were censored on the day of bail-out (hypothetical estimand). |
| Secondary | Number of Subjects With Major Bleeding Events (MBE) at Day 6 | From start of treatment (Alteplase) or randomisation (SOC) (day 1) till Day 6, up to 6 days. | Number of subjects with major bleeding events (MBE). Major bleeding events (MBE) according to International Society on Thrombosis and Haemostasis \[ISTH\] definition until Day 6. Definition of a major bleed: •Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or •Bleeding associated with a reduction in hemoglobin of at least 2 gram/deciliter (1.24 millimole/Liter), or leading to transfusion of two or more units of blood or packed cells and/or •Fatal bleed |
| Secondary | All Cause Mortality at Day 28 | Up to 28 days. | All cause mortality at Day 28. If it is unknown whether the patient was dead at end of Day 28, then it will be assumed that the patient did not die up to Day 28, regardless of the reason. This unfavorable endpoint is met if: * the last known status of the patient is 10 on the WHO clinical progression scale by the end of Day 28, or * vital status is dead within 28 days |
| Secondary | Number of Subjects With Treatment Failure at Day 28 | Up to 28 days. | Treatment failure defined as all cause mortality or mechanical ventilation at Day 28. |
| Secondary | Number of Ventilator-free Days at Day 28 | Up to 28 days. | Number of ventilator-free days (VFDs) from start of treatment to Day 28. 'Ventilator' is defined as 'assisted breathing' but it refers to mechanical invasive ventilation. The number of VFDs starts from when the patient has a 'lasting' value on the WHO clinical progression scale of ≤ 6, and ends on Day 28. A lasting value of ≤ 6 means that the value cannot exceed 6 at a later timepoint. If the patient is liberated from the ventilator on Day x, then the number of VFDs is 28-x. If a patient has withdrawn consent prior to day 28 then he will have a missing value for VFD. In any case, if the status of the patient at Day 28 is death, as determined from the vital status page then the VFD=0. |
| Secondary | Number of Subjects With Improvement of Sequential (Sepsis-related) Organ Failure Assessment (SOFA) Score by ≥2 Points at Day 6 | Baseline (Day 0) and Day 6 of treatment | Number of subjects with improvement of Sequential (sepsis-related) Organ Failure Assessment (SOFA) score by ≥2 points from baseline to end of Day 6. The Sequential Organ Failure Assessment (SOFA) scores six variables: respiratory, coagulation, liver, Cardiovascular, central nervous system and renal. Each variable is score from 0 (best outcome) to 4 (worst outcome) with a total score calculated as the sum of all six variables ranging from 0 (best outcome) to 24 (worst outcome). |
| Secondary | Daily Average PaO2/FiO2 Ratio Change From Baseline to Day 6 | Up to 6 days. | Daily average PaO2/FiO2 ratio (or inferred PaO2/FiO2 ratio from SpO2) change from baseline to Day 6. This assessment was measured approximately 3-times daily. All available values on each of these days, regardless of the position of the patient when being measured, were averaged in order to determine the daily average PaO2/FiO2 ratio for that patient. The higher the value the better the health status of the patient. If the patient was still in hospital during day 6 then the day 6 daily average value was used, if available. If the patient was discharged from hospital prior to day 6 then the daily average at the time of hospital discharge was used as a surrogate for day 6, if available. If the patient died prior to day 6 then there was no imputation but the death handled as failure in the determination of the difference in medians and 95% CI. Based upon this, the change from baseline for each patient was calculated. |
| Secondary | Number of Oxygen-free Days up to Day 28 | Up to 28 days. | Number of oxygen-free days (OFD) up to Day 28. Oxygen-free is defined as free from assistance from oxygen support. The number of oxygen-free days starts from when the patient has a 'lasting' value on the WHO clinical progression scale of ≤ 4 and ends on Day 28. A lasting value of ≤ 4 means that the value cannot exceed 4 at a later timepoint. If the patient is liberated from oxygen on Day x, then the number of OFDs is 28-x. If a patient has withdrawn consent prior to day 28 then he will have a missing value for OFD. In any case, if the status of the patient at Day 28 is death, as determined from the vital status page then the OFD=0. |
| Secondary | Length of Hospital Stay up to Day 28 | Up to 28 days. | Length of hospital stay up to day 28 was determined based upon the first hospital discharge date, or discharge to another care facility. If the patient died within the first 28 day period, then length of hospital stay was 28. |
| Secondary | Worst PaO2/FiO2 Ratio Change From Baseline to Day 6 | Up to 7 days. | Worst PaO2/FiO2 ratio (or inferred PaO2/FiO2 ratio from SpO2) change from baseline to day 6. This assessment was planned to be measured on each of days 0 to 6. but only whilst the patients was still in hospital. The worst (lowest) daily measurement will be used and the higher the value the better the health status of the patient. * If the patient was still in hospital during day 6 then the day 6 value was used * If the patient was discharged from hospital prior to day 6 then the value at the time of hospital discharge was used * If the patient died prior to day 6 then the last value prior to death was used * If day 6 value was missing but Day 5 value available, the day 5 value was used * If day 6 value was missing, no Day 5 value available, but day 7 available, then day 7 value was used * Otherwise value was set to missing for that patient. Based upon this, the change from baseline for each patient was calculated and used for the analysis. |
Source ClinicalTrials.gov
Outcomes10
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Time to Clinical Improvement or Hospital Discharge up to Day 28 | Up to 28 days. | Full Analysis Set (FAS) consisted of all randomised patients with at least one baseline and one post baseline assessment relating to the primary endpoint. | days | MEDIAN |
| SECONDARY | Number of Subjects With Major Bleeding Events (MBE) at Day 6 | From start of treatment (Alteplase) or randomisation (SOC) (day 1) till Day 6, up to 6 days. | The Treated Set (TS) consisted of all patients who were randomised and, for patients in the alteplase groups, treated with at least one dose of trial drug. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | All Cause Mortality at Day 28 | Up to 28 days. | Full Analysis Set (FAS) consisted of all randomised patients with at least one baseline and one post baseline assessment relating to the primary endpoint. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Subjects With Treatment Failure at Day 28 | Up to 28 days. | Full Analysis Set (FAS) consisted of all randomised patients with at least one baseline and one post baseline assessment relating to the primary endpoint. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Ventilator-free Days at Day 28 | Up to 28 days. | Full Analysis Set (FAS) consisted of all randomised patients with at least one baseline and one post baseline assessment relating to the primary endpoint. The endpoint was only planned for subjects in Part 1. | Days | MEAN |
| SECONDARY | Number of Subjects With Improvement of Sequential (Sepsis-related) Organ Failure Assessment (SOFA) Score by ≥2 Points at Day 6 | Baseline (Day 0) and Day 6 of treatment | Full Analysis Set (FAS) consisted of all randomised patients with at least one baseline and one post baseline assessment relating to the primary endpoint. The endpoint was only planned for subjects in Part 1. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Daily Average PaO2/FiO2 Ratio Change From Baseline to Day 6 | Up to 6 days. | Full Analysis Set (FAS) consisted of all randomised patients with at least one baseline and one post baseline assessment relating to the primary endpoint. Only subjects with non-missing endpoint data were included. The endpoint was only planned for subjects in Part 1. | PaO2/FiO2 ratio | MEDIAN |
| SECONDARY | Number of Oxygen-free Days up to Day 28 | Up to 28 days. | Full Analysis Set (FAS) consisted of all randomised patients with at least one baseline and one post baseline assessment relating to the primary endpoint. The endpoint was only planned for subjects in Part 2. | Days | MEDIAN |
| SECONDARY | Length of Hospital Stay up to Day 28 | Up to 28 days. | Full Analysis Set (FAS) consisted of all randomised patients with at least one baseline and one post baseline assessment relating to the primary endpoint. The endpoint was only planned for subjects in Part 2. | Days | MEDIAN |
| SECONDARY | Worst PaO2/FiO2 Ratio Change From Baseline to Day 6 | Up to 7 days. | Full Analysis Set (FAS) consisted of all randomised patients with at least one baseline and one post baseline assessment relating to the primary endpoint. The endpoint was only planned for subjects in Part 2. | PaO2/FiO2 ratio | MEAN |
Source ClinicalTrials.gov
Results by group49
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Time to Clinical Improvement or Hospital Discharge up to Day 28 | Part 1: Alteplase Low Dose | NA | 95% Confidence Interval 14.0 to NA | days | |
| Time to Clinical Improvement or Hospital Discharge up to Day 28 | Part 1: Alteplase High Dose | 19.0 | 95% Confidence Interval 9.0 to NA | days | |
| Time to Clinical Improvement or Hospital Discharge up to Day 28 | Part 1: Standard of Care | NA | 95% Confidence Interval 17.0 to NA | days | |
| Time to Clinical Improvement or Hospital Discharge up to Day 28 | Part 2: Alteplase High Dose - Non-invasive Mechanical Ventilation (NIV) Patients | 22.0 | 95% Confidence Interval 7.0 to NA | days | |
| Time to Clinical Improvement or Hospital Discharge up to Day 28 | Part 2: Standard of Care - Non-invasive Mechanical Ventilation (NIV) Patients | NA | 95% Confidence Interval 8.0 to NA | days | |
| Time to Clinical Improvement or Hospital Discharge up to Day 28 | Part 2: Alteplase High Dose - Invasive Mechanical Ventilation (IMV) Patients | 25.5 | 95% Confidence Interval 13.0 to NA | days | |
| Time to Clinical Improvement or Hospital Discharge up to Day 28 | Part 2: Standard of Care - Invasive Mechanical Ventilation (IMV) Patients | NA | 95% Confidence Interval 4.0 to NA | days | |
| Number of Subjects With Major Bleeding Events (MBE) at Day 6 | Part 1: Alteplase Low Dose | 1 | Participants | ||
| Number of Subjects With Major Bleeding Events (MBE) at Day 6 | Part 1: Alteplase High Dose | 4 | Participants | ||
| Number of Subjects With Major Bleeding Events (MBE) at Day 6 | Part 1: Standard of Care | 0 | Participants |
1 to 10 of 49Source ClinicalTrials.gov
See all 49 results by groupParticipant flow21
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Part 1: Alteplase Low Dose | 20 | |
| Overall Study | STARTED | Part 1: Alteplase High Dose | 20 | |
| Overall Study | STARTED | Part 1: Standard of Care | 22 | |
| Overall Study | STARTED | Part 2: Alteplase High Dose - Non-invasive Mechanical Ventilation (NIV) Patients | 17 | |
| Overall Study | STARTED | Part 2: Standard of Care - Non-invasive Mechanical Ventilation (NIV) Patients | 8 | |
| Overall Study | STARTED | Part 2: Alteplase High Dose - Invasive Mechanical Ventilation (IMV) Patients | 12 | |
| Overall Study | STARTED | Part 2: Standard of Care - Invasive Mechanical Ventilation (IMV) Patients | 5 | |
| Overall Study | COMPLETED | Part 1: Alteplase Low Dose | 17 | |
| Overall Study | COMPLETED | Part 1: Alteplase High Dose | 12 | |
| Overall Study | COMPLETED | Part 1: Standard of Care | 22 |
1 to 10 of 21Source ClinicalTrials.gov
See all 21 participant flowAdverse events1,008
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Part 1: Alteplase Low Dose | 0 | 20 | |
| other | Anaemia | Blood and lymphatic system disorders | Part 1: Alteplase High Dose | 1 | 20 | |
| other | Anaemia | Blood and lymphatic system disorders | Part 1: Standard of Care | 0 | 22 | |
| other | Anaemia | Blood and lymphatic system disorders | Part 2: Alteplase High Dose - Non-invasive Mechanical Ventilation (NIV) Patients | 2 | 17 | |
| other | Anaemia | Blood and lymphatic system disorders | Part 2: Standard of Care - Non-invasive Mechanical Ventilation (NIV) Patients | 0 | 8 | |
| other | Anaemia | Blood and lymphatic system disorders | Part 2: Alteplase High Dose - Invasive Mechanical Ventilation (IMV) Patients | 1 | 12 | |
| other | Anaemia | Blood and lymphatic system disorders | Part 2: Standard of Care - Invasive Mechanical Ventilation (IMV) Patients | 1 | 5 | |
| other | Arrhythmia | Cardiac disorders | Part 1: Alteplase Low Dose | 0 | 20 | |
| other | Arrhythmia | Cardiac disorders | Part 1: Alteplase High Dose | 0 | 20 | |
| other | Arrhythmia | Cardiac disorders | Part 1: Standard of Care | 0 | 22 |
1 to 10 of 1,008Source ClinicalTrials.gov
See all 1,008 adverse eventsAdverse event totals21
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Part 1: Alteplase Low Dose | 6 | 20 |
| Total, all-cause mortality | Part 1: Alteplase High Dose | 6 | 20 |
| Total, all-cause mortality | Part 1: Standard of Care | 9 | 22 |
| Total, all-cause mortality | Part 2: Alteplase High Dose - Non-invasive Mechanical Ventilation (NIV) Patients | 2 | 17 |
| Total, all-cause mortality | Part 2: Standard of Care - Non-invasive Mechanical Ventilation (NIV) Patients | 3 | 8 |
| Total, all-cause mortality | Part 2: Alteplase High Dose - Invasive Mechanical Ventilation (IMV) Patients | 3 | 12 |
| Total, all-cause mortality | Part 2: Standard of Care - Invasive Mechanical Ventilation (IMV) Patients | 2 | 5 |
| Total, other adverse events | Part 1: Alteplase Low Dose | 11 | 20 |
| Total, other adverse events | Part 1: Alteplase High Dose | 11 | 20 |
| Total, other adverse events | Part 1: Standard of Care | 12 | 22 |
1 to 10 of 21Source ClinicalTrials.gov
See all 21 adverse event totalsPapers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 39522090 | DERIVED |
Source PubMed
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
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