Efficacy of DEXamethasone in Patients With Acute Hypoxemic REspiratory Failure Caused by INfEctions (DEXA-REFINE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Consorcio Centro De Investigacion Biomedica En Red

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

20 Dec 2024 → ongoing

Decision date (initial)

2024-12-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519759-27-00

EudraCT number

2020-001278-31

ClinicalTrials.gov

NCT04545242

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

The effects 20/10 mg vs. 6 mg of intravenous dexamethasone on the number of deaths at 60 days after randomization and the number of days alive without ventilator support at 28 days, and other subjectcentered outcomes in adult subjects with AHRF (including ARDS) caused by pulmonary or systemic infections (including COVID-19). Death from any cause 60 days after randomization. Death, if occurred, will be recorded irrespective whether the subject remains in the same hospital, in another health care facility, or discharged home. If subjects are discharged alive from hospital before day 60, clinical status information at 60 days will be obtained from the electronic clinical record.

Secondary objectives 4

1. Number of ventilator-free days (VFDs) at 28 days after randomization. Similarly to what has been recently recommended (45), the following considerations will be made for calculating number of VFDs: successful liberation from MV should last more than 48 hours without reintubation in subjects who have survived 28 days after randomization (extubation will be counted from the last successful attempt in subjects who have survived 28 days since randomization) and for subjects ventilated for 28 days or more or who died before 28 days (irrespective of intubation status), the number of VFDs will be recorded as zero.
2. Number of subjects with one or more serious adverse reactions (SARs) at day 28 defined as new episodes of sepsis/septic shock, new pneumonia, reintubation, clinically important gastrointestinal bleeding, or anaphylactic reaction to dexamethasone.
3. All-cause ICU mortality.
4. All-cause hospital mortality.

Conditions and MedDRA coding

Acute Hypoxemic Respiratory Failure

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age ≥18 years.
2. Intubated and mechanically ventilated, defined as requiring ventilatory support at the time of Screening.
3. Acute onset of AHRF (as defined by a PaO2/FiO2 ≤300 mmHg during at least 6 hours from diagnosis. For the measurement of PaO2 and calculation of PaO2/FiO2 ratio, the minimum accepted value for PEEP is 5 cmH2O and for FiO2 is 0.3. ARDS is defined by Berlin criteria,4 which includes: (i) having pneumonia or worsening respiratory symptoms, (ii) bilateral pulmonary infiltrates on chest imaging (x-ray or CT scan), (iii) absence of left atrial hypertension or no clinical signs of left heart failure, and (iv) hypoxemia, as defined by a PaO2/FiO2 ≤300 mmHg on positive end-expiratory pressure (PEEP) of ≥5 cmH2O, regardless of FiO2.
4. Pulmonary or systemic infectious etiology of AHRF.

Exclusion criteria 6

1. Subjects with a known contraindication to corticosteroids or know hypersensitivity. History of any hypersensitivity reaction to dexamethasone, including but not limited to urticaria, eczema, angioedema, bronchospasm, and anaphylaxis.
2. Subjects who have an indication of chronic use of higher doses of systemic corticosteroids. Use of systemic corticosteroids in doses higher than 6 mg dexamethasone equivalents for other indications than COVID- 19: systemic corticosteroids in doses higher than 6 mg dexamethasone / 6 mg betamethasone / 200 mg cortisone / 160 mg hydrocortisone / 32 mg methylprednisolone / 40 mg prednisolone / 40 mg prednisone.
3. Subjects who have received corticosteroids for 5 consecutive days or more up to the day of screening.
4. Pregnant woman.
5. Participation in another therapeutic trial study that collide.
6. Lack of informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. All-cause hospital mortality.

Secondary endpoints 6

1. Number of ventilator free-days (VFDs) at Day 28 (defined as days alive and free from mechanical ventilation at day 28 after intubation. For subjects ventilated >=28 days and for subjects who die, VFD is 0.
2. Mortality at ICU and at Day 28.
3. Duration (in days) on mechanical ventilation.
4. Length of stay (in days) in the hospital for survivors.
5. Time (in days) from treatment initiation to death.
6. Proportions with viral RNA detection over time.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Consorcio Centro De Investigacion Biomedica En Red

Sponsor organisation

Consorcio Centro De Investigacion Biomedica En Red

Address

Pab 11, Avenida De Monforte De Lemos 3-5 Avenida De Monforte De Lemos 3-5

City

Madrid

Postcode

28029

Country

Spain

Scientific contact point

Organisation

Consorcio Centro De Investigacion Biomedica En Red

Contact name

Projects Department

Public contact point

Organisation

Consorcio Centro De Investigacion Biomedica En Red

Contact name

Projects Department

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 14 files

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

Application history

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