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

Nantes University Hospital (NUH)

Status and phase

Unknown

Phase 2

Conditions

Critically Ill Patients

Treatments

Drug: Recombinant Interferon gamma 1b placebo

Drug: Recombinant Interferon gamma 1b (IMUKIN®)

Study type

Interventional

Funder types

Other

Identifiers

NCT04793568

RC20_0082

Details and patient eligibility

About

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.

Full description

200 adult patients hospitalized in intensive care units, under mechanical ventilation in three European countries will be included in the trial, and will be randomized in 2 arms :

Arm 1 (rHu-IFNγ):

• Recombinant Interferon gamma 1b (IMUKIN®, from Clinigen®): 100 µg/0,5ml subcutaneous injections from day 1 to day 9 (5 injections, i.e. 1 injection of 100 µg every 48h),

Arm 2 (Placebo):

• Recombinant Interferon gamma 1b placebo: 5 subcutaneous injections from day 1 to day 9 (i.e. 1 injection of 0,5ml every 48h).

Enrollment

109 patients

Sex

All

Ages

18 to 85 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Adult patients (18yr to 85yr).
Hospitalized in intensive care unit for less than 48 hours.
Receiving invasive mechanical ventilation at the time of inclusion.
One or more acute organ failure at the time of inclusion among: neurological (Glasgow coma scale <13 before sedation), hemodynamic (norepinephrine, epinephrine, or any other vasopressor at a dose of ≥ 0.1 μg per kilogram of body weight per minute or ≥0.5 mg per hour for at least 6 hours), respiratory (PaO2 / FiO2< 200) and/or renal (creatininemia > 2 fold higher than the basal value and/or oliguria < 0.5 mL/kg/hour for at less 12 hours).
Informed consent from a legal representative, or emergency procedure (when possible according to national regulation, see below). As is not possible to obtain the patient consent prior the inclusion (comatose patients), patient consent for the study continuation will be obtained as soon as deemed possible.
Person insured under a health insurance scheme.

Exclusion criteria

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)
Immunosuppression (hematologic cancer, aplasia, chemotherapy/radiotherapy for cancer within 3 months prior to the inclusion, known infection Human immunodeficiency virus, concomitant use of any anti-graft rejection drug).
Coma after resuscitated cardiac arrest
Cervical spinal cord injury
Participation to a drug interventional study within 1 month prior to the inclusion
Hospital-acquired pneumonia before inclusion in the study during the current hospitalization.
Sustained hyperlactatemia > 5 mmol/L.