Baricitinib for treating hospital-acquired pneumonia in critically ill patients with a proinflammatory phenotype, an international phase II / phase III, randomized, controlled trial - the TREAT-HAP study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nantes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Decision date (initial)

2023-07-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

European Commission

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objectives of this randomized trial are first to determine the safety (phase II), then efficacy (phase III) of baricitinib plus standard of care (SOC) as compared to SOC alone for the treatment of hospital-acquired pneumonia in patients with a pro-inflammatory profile.

Secondary objectives 6

1. To demonstrate the efficacy of baricitinib on pneumonia-associated morbidity and mortality reduction
2. To describe the safety of baricitinib
3. To assess the economic efficiency of baricitinib compared to standard of care
4. To assess the suitability and acceptability of baricitinib from the patients’ perspectives
5. To develop biomarkers for the stratification of patients into responders and non-responders to baricitinib
6. To create a biobank of blood and respiratory samples collected from humans with hospital-acquired pneumonia

Conditions and MedDRA coding

Hospital-acquired pneumonia

Regulatory references

Scientific advice from competent authorities

National Agency For The Safety Of Medicine And Health Products

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Adult patients (18yr to 85yr)
2. Ventilator-associated pneumonia (VAP) or hospital-acquired pneumonia requiring invasive ventilation (V-HAP)
3. Biological systemic inflammatory response defined according to the on-site standard of care
4. Receiving antimicrobial therapy for the current episode of HAP pneumonia for less than 72 hours
5. Informed consent from a legal representative, or emergency procedure (when possible, according to national regulation, see below). If it is impossible to obtain patient consent before the inclusion (comatose patients), patient consent for the study continuation will be obtained as soon as deemed possible
6. Person insured under a health insurance scheme

Exclusion criteria 14

1. Pregnant women (serum or urine test), breastfeeding women
2. Participation to an interventional drug study within 1 month before to the inclusion
3. Patient under legal protection (incl. under guardianship or trusteeship)
4. Hypersensitivity to baricitinib
5. Uncontrolled herpes zoster, active viral hepatitis, infection with human immunodeficiency virus, active fungal infections, or active tuberculosis
6. Severe hepatic insufficiency (Child-Pugh B or C)
7. Acute or chronic renal insufficiency (Modification of Diet in Renal Disease (MDRD) Creatinine Clearance < 30 ml/min/1.73m2) or renal replacement therapy
8. Persistent anemia (haemoglobin < 8 g/L), lymphopenia (absolute lymphocyte < 500 cells/mm3), or neutropenia (absolute neutrophil count <1,000 cells/mm3)
9. Immunosuppression (hematologic cancer, aplasia, chemotherapy/radiotherapy for cancer within 3 months prior to the inclusion, or anti-graft rejection drug)
10. Recent (<90 days) thromboembolic event
11. Active COVID 19 pneumonia ( PCR or antigen detection within the last 7 days)
12. chronic or recurrent infection
13. cancer in the last year
14. active long time smokers ( > 20 years)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The co-primary hierarchic endpoints to demonstrate the efficacy of baricitinib plus standard of care (SOC) compared to SOC for the treatment of hospital-acquired pneumonia will be a clinical cure at the test-of-cure (TOC) visit and all-cause mortality at Day 28.

Secondary endpoints 4

1. In case of non-significative difference in the rate of clinical cure, the co-primary outcome (all-cause mortality at Day 28) will be presented as a secondary outcome
2. The secondary outcomes to determine the safety of baricitinib are rate of serious adverse effects and suspected unexpected serious adverse reaction (SUSAR) at Day 28
3. The secondary outcomes to determine if baricitinib increases the economic efficiency of the treatment of pneumonia are the economic endpoints at 6 months, Incremental cost-effectiveness ratio (ICER).
4. The secondary outcomes to determine the suitability and acceptability of baricitinib from the patients’ perspectives are changes in health-related quality of life (HRQoL) from three (M3) to six months (M6) after randomization measured with SF-36, HADS and SWLS.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nantes

Sponsor organisation

Centre Hospitalier Universitaire De Nantes

Address

1 Place Alexis Ricordeau

City

Nantes

Postcode

44000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Prof. Antoine ROQUILLY

Public contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Prof. Antoine ROQUILLY

Locations

4 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Application history

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