Clinical Trial with Aprotinin in the Acute Respiratory Distress Syndrome Treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Del Hospital Nacional De Paraplejicos Para La Investigacion Y La Integracion

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2025-08-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective of this study is to demonstrate the efficacy of aprotinin in improving clinical outcome and the need for mechanical ventilation in patients with moderate or severe ARDS.

Secondary objectives 12

1. To evaluate the safety of aprotinin compared to placebo.
2. To evaluate the 28-day all-cause mortality of aprotinin compared with placebo.
3. To evaluate all-cause mortality at other selected time points.
4. To evaluate the efficacy of aprotinin compared to placebo by assessing: - Mechanical ventilation-free days. - Number of ICU-free days. - Number of days of hospitalization. - To evaluate the dose escalation and pharmacodynamics (PD) of aprotinin. - To assess patient outcomes in terms of respiratory performance (forced expiratory volume in 1 second [FEV1]).
5. Evaluate selected pharmacoeconomic parameters.
6. To assess gas exchange (partial pressure of oxygen/inspired oxygen fraction [PaO2/FiO2] ratio) during mechanical ventilation as an indicator of improved lung function with treatment.
7. To evaluate possible selected inflammatory markers.
8. Obtain bronchial brush-derived granular proteins (collected by fibrobronchoscopy prior to initiation of treatment) to determine possible phenotypes and response to treatment.
9. To determine bradykinin and kallikrein levels in both bronchial brushings and plasma as a measure of efficacy of aprotinin treatment.
10. Determine plasma inflammatory markers (pro- and anti-inflammatory cytokines).
11. Determine plasma aprotinin levels in plasma.
12. Obtain a blood sample for future pharmacogenetic analysis.

Conditions and MedDRA coding

ACUTE RESPIRATORY DISTRESS SYNDROME

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. The patient has a diagnosis of moderate or severe ARDS according to the Berlin definition of ARDS (Ref: ARDS Definition Task Force 2012): 1.1 Acute onset of respiratory failure within 1 week of a known clinical insult or new or worsening respiratory symptoms. 1.2 Respiratory failure associated with known ARDS risk factors and not fully explained by either heart failure or fluid overload (objective assessment of heart failure or fluid overload is required if there are no risk factors for ARDS [moderate or severe ARDS].
2. The radiological and hypoxemia criteria (1.3 and 1.4) must occur within the same 24-hour period. The time of onset of ARDS is when the last of the two specified ARDS criteria is met.
3. Administration of the first dose of study drug should be planned to occur within 48 hours of the diagnosis of moderate or severe ARDS.
4. The patient is intubated and receiving mechanical ventilation.
5. The patient is aged ≥18 years.

Exclusion criteria 13

1. Woman known to be pregnant, breastfeeding, or with a positive (urine or serum test) or indeterminate (serum test) pregnancy test.
2. The patient is concurrently participating in another pharmacotherapeutic protocol.
3. The patient is not expected to survive for 24 hours.
4. The patient has an underlying clinical condition in which, in the opinion of the investigator, withdrawal of ventilation would be extremely unlikely, e.g., motor neuron disease, Duchenne muscular dystrophy, or rapidly progressive interstitial pulmonary fibrosis.
5. The patient has severe chronic obstructive pulmonary disease requiring long-term home oxygen therapy or mechanical ventilation (noninvasive ventilation or by tracheostomy), except continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BIPAP) used only for sleep disordered breathing.The patient has congestive heart failure, defined as New York Heart Association class IV (Reference: Committee for Medicinal Products for Human Use 1994).
6. The patient has acute left ventricular failure.
7. The patient has hepatic failure (Child-Pugh grade C).
8. The patient has received any previous IFN.
9. The patient has known hypersensitivity to natural or recombinant IFN beta or to any of the excipients.
10. The patient is receiving renal dialysis therapy due to chronic renal insufficiency.
11. 11. The patient is receiving extracorporeal membrane oxygenation, high frequency oscillatory ventilation (HFOV) or any form of extracorporeal lung assist.
12. The patient has received any form of mechanical ventilation (invasive or noninvasive, excluding CPAP alone) for more than 48 hours prior to the diagnosis of ARDS. Non-invasive ventilation has to be applied continuously for at least 12 hours per day during those 48 hours.
13. The patient has burns on ≥15% of his total body surface area.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. primary efficacy: For the primary endpoint, ventilator-free days (DLVI) will be calculated. A patient will be considered ventilator-free after two consecutive calendar days of unassisted ventilation. These variables will also be assessed at D90 in an exploratory analysis.

Secondary endpoints 4

1. secondary efficacy: All-cause mortality will be assessed at D28 (primary) and also at D90 and D180. All deaths will be recorded as EAS up to D180. The location of the patient at the time of death (ICU or hospital) will also be recorded. SOFA, renal support, vasoactive support, respiratory functioning, persistent weakness and neuropsychological disorders (D180).
2. safety: Adverse Event Evaluation, Causality, Adverse Event in Clinical Laboratory, Adverse Event Recording, Serious Adverse Event Reporting, Adverse Event Follow-Up, Adverse Event Monitoring
3. laboratory: Blood samples will be taken for biochemistry and hematology at screening, prior to dosing on D1 (baseline) and daily until D28 while the patient is in the ICU.
4. vital signs: - Blood pressure (systolic, diastolic and mean; mmHg): to be recorded through an arterial line. - Heart rate (HR; bpm): measured according to clinical practice in each ICU. - Total respiratory rate (breaths per minute). - Temperature (°C) - ECG

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Del Hospital Nacional De Paraplejicos Para La Investigacion Y La Integracion

Sponsor organisation

Fundacion Del Hospital Nacional De Paraplejicos Para La Investigacion Y La Integracion

Address

Finca La Peraleda S/N

City

Toledo

Postcode

45071

Country

Spain

Scientific contact point

Organisation

Fundacion Del Hospital Nacional De Paraplejicos Para La Investigacion Y La Integracion

Contact name

Francisco Javier Redondo Calvo

Public contact point

Organisation

Fundacion Del Hospital Nacional De Paraplejicos Para La Investigacion Y La Integracion

Contact name

Francisco Javier Redondo Calvo

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications