Human Recombinant Interferon Gamma-1b for the Prevention of Hospital-acquired Pneumonia in Critically Ill Patients: a Double-blind, International, Phase 2, Randomized, Placebo-controlled Trial - the PREV-HAP Study

NCT04793568 | Unknown Phase 2 DMC

• 1 other identifier: RC20_0082
• Study Type: interventional
• Target: 109
• Locations: 3 countries
• Sites: 18

Brief Summary

PREV-HAP study is part of a larger project entitled 'Host-targeted Approaches for the Prevention and the treatment of Hospital-Acquired Pneumonia' (HAP2), funded by the European Union's H2020 research and innovation programme under grant agreement N°847782. HAP2 aims to develop stratified host-directed drugs and biomarkers to enhance the prevention and the treatment of HAP and develop precision medicine in infectious diseases. Its ambition is to revolutionize the management of HAP: capitalising on the novel concept of critical-illness related immunosuppression altering the host-pathogens interactions, the aim is to propose a complete reappraisal of the physiopathology of HAP based on the concept of respiratory dysbiosis. The main hypothesis of the PREV-HAP study is that human recombinant Interferon gamma 1b (rHuIFN-γ, Imukin) treatment can restore immunity in critically ill patients and prevent Hospital-Acquired Pneumonia. The hypothesesis is that the in vivo investigations of the host-pathogens interactions can be used for the stratification of patients into high/low risk and responders/non-responders to host-targeted prevention of hospital-acquired infections. The involvement of a state of critical-illness related immunosuppression in the susceptibility to hospital-acquired pneumonia is widely accepted, and an emerging trend is that the development of drugs for the treatment of this acquired immunosuppression will prevent infection and enhance outcomes of hospitalized patients. It has been demonstrated that the productions of IFN-γ by immune cells are decreased in critically ill patients, and that these defects are associated with the susceptibility to HAP. rHuIFN-γ has neither been tested nor is recommended as adjunctive treatment of patients with HAP. Based on these specific factors identified in the host response, it is proposed in this study to use rHuIFN-γ as novel preventive approach for HAP.

Conditions

Critically Ill Patients

Outcome Measures

Primary Outcomes (1)

• To demonstrate the efficiency of rHuIFN-γ for the prevention of hospital-acquired pneumonia

  Rate of the composite outcome at day 28 made of at least one item among the following: all cause mortality and/or hospital-acquired pneumonia

  Day 28

Secondary Outcomes (28)

• All-cause mortality [efficiency of rHu-IFN-γ, on pneumonia-associated morbidity and mortality reduction]

  Day 28 and Day 90

• Rate of HAP [efficiency]

  Day 28

• Bacterial ecology of the 1st episode of HAP [efficiency]

  Day 28

• Rate of ventilator-associated tracheobronchitis [efficiency]

  Day 28

• Occurence of Acute Respiratory Distress Syndrome [efficiency]

  Day 28

Study Arms (2)

Recombinant Interferon gamma 1b (IMUKIN®)

EXPERIMENTAL

Drug: Recombinant Interferon gamma 1b (IMUKIN®)

Recombinant Interferon gamma 1b placebo

PLACEBO COMPARATOR

Drug: Recombinant Interferon gamma 1b placebo

Interventions

Recombinant Interferon gamma 1b (IMUKIN®) DRUG

100 µg/0,5ml subcutaneous injections from day 1 to day 9 (5 injections, i.e. 1 injection of 100 µg every 48h)

Recombinant Interferon gamma 1b (IMUKIN®)

Recombinant Interferon gamma 1b placebo DRUG

5 subcutaneous injections from day 1 to day 9 (i.e. 1 injection of 0,5ml every 48h).

Recombinant Interferon gamma 1b placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (18yr to 85yr).
• Hospitalized in intensive care unit for less than 48 hours.
• Person insured under a health insurance scheme.

You may not qualify if:

• Pregnant women (serum or urine test), breastfeeding women
• Patient under legal protection (incl. under guardianship or trusteeship)
• Hypersensitivity to the active substance (interferon gamma-1b) or known hypersensitivity to related products, such as another interferon, or to any of the following excipients: Mannitol, Disodium succinate hexahydrate, Succinic acid, Polysorbate 20
• Severe hepatic insufficiency ( Child Pugh score B or C)
• Liver cytolysis with hepatic enzymes (AST and/or ALT) \> 5N
• Severe chronic renal insufficiency (MDRD Creatinine Clearance \< 10 ml/min/1.73m2)
• Coma after resuscitated cardiac arrest
• Cervical spinal cord injury
• Sustained hyperlactatemia \> 5 mmol/L.

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (18)

Angers University Hospital

Angers, France

Location

Argenteuil Hospital

Argenteuil, France

Location

Brest University Hospital

Brest, France

Location

Beaujon University Hospital

Clichy, France

Location

Limoges University Hospital

Limoges, France

Location

Nantes University Hospital

Nantes, 44093, France

Location

Rennes University Hospital

Rennes, France

Location

Aghioi Anargyroi General Oncology Hospital

Athens, Greece

Location

Attikon University General Hospital

Athens, Greece

Location

General University Hospital of Heraklion

Heraklion, Greece

Location

University General Hospital of Ioannina

Ioannina, Greece

Location

General University Hospital of Larissa

Larissa, Greece

Location

Koutlimbaneio & Triantafylleio General Hospital of Larissa

Larissa, Greece

Location

Hospital Clínic Barcelona

Barcelona, Spain

Location

Hospital Vall d'Hebron

Barcelona, Spain

Location

Hôpital universitaire Arnau de Vilanova

Lleida, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Universitario de Son Llátzer

Palma, Spain

Location

Related Publications (4)

• Anani H, Destras G, Regue H, Bulteau S, Bressollette-Bodin C, Roquilly A, Josset L. Metagenome-assembled complete genome of Bohxovirus, a virulent bacteriophage involved in the prediction of hospital-acquired pneumonia in intubated critically ill patients. Microbiol Resour Announc. 2025 Dec 11;14(12):e0059225. doi: 10.1128/mra.00592-25. Epub 2025 Oct 29.

  PMID: 41159973 DERIVED

• Bulteau S, Braud M, Petrier M, Castain L, Anani H, Peltier C, Mobuchon L, Bouras M, Flattres D, Poschmann J, Josset L, Roquilly A, Bressollette-Bodin C. Interferon Gamma Injection and Its Effect on the Respiratory Anelloviridae Population in ICU Ventilated Patients. J Med Virol. 2025 Oct;97(10):e70612. doi: 10.1002/jmv.70612.

  PMID: 41036698 DERIVED

• Anani H, Destras G, Bulteau S, Castain L, Semanas Q, Burfin G, Petrier M, Martin FP, Poulain C, Dickson RP, Bressollette-Bodin C, Roquilly A, Josset L. Lung virome convergence precedes hospital-acquired pneumonia in intubated critically ill patients. Cell Rep Med. 2025 Sep 16;6(9):102289. doi: 10.1016/j.xcrm.2025.102289. Epub 2025 Sep 5.

  PMID: 40914165 DERIVED

• Bouras M, Tessier P, Poulain C, Schirr-Bonnans S, Roquilly A. Three-month outcomes and cost-effectiveness of interferon gamma-1b in critically ill patients: a secondary analysis of the PREV-HAP trial. J Intensive Care. 2024 Oct 11;12(1):40. doi: 10.1186/s40560-024-00753-z.

  PMID: 39394183 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: March 11, 2021
• Study Start: March 29, 2021
• Primary Completion: November 7, 2021
• Study Completion: June 1, 2023
• Last Updated: February 16, 2022

Record last verified: 2022-02

Locations

FR (7); GR (6); ES (5)