Intravenous N-acetylcysteine and Oseltamivir Versus Oseltamivir in Adults Hospitalized With Influenza and Pneumonia

The Chinese University of Hong Kong

Status and phase: Enrolling; Phase 3

Conditions: Influenza

Treatments: Drug: 5% Dextrose; Drug: N-acetyl cysteine

Study type: Interventional

Funder types: Other

Identifiers

NCT03900988

NAC Influenza/Hui/2019

Details and patient eligibility

About

Seasonal influenza epidemics are important causes of morbidity and mortality. Cytokine dysregulation, with high levels of pro-inflammatory cytokines, occurs in patients with severe influenza. Early therapy with a neuraminidase inhibitor (NAI) is associated with better outcome in patients hospitalized with influenza, but significant mortality occurs despite use of antivirals. N-acetylcysteine (NAC) is a modified form of the amino acid cysteine, with anti-oxidant properties. NAC was shown to inhibit the production of pro-inflammatory molecules in lung epithelial cells infected with influenza viruses. Previous case report showed that high dose NAC, administered as continuous intravenous infusion, was effective and safe in improving the clinical outcomes. We aim to perform a randomized controlled trial to evaluate the therapeutic role of adjunctive NAC in the clinical management of patients with influenza complicated by lower respiratory tract involvement and abnormal respiratory status. Such information when available may reveal the potential of NAC for optimization of management of severe influenza, and provide important insights into future adjunctive therapy research.

Enrollment: 160 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• influenza A and B virus infections confirmed by polymerase chain reaction (PCR) and/or immunofluorescence assays,
• hospitalized for the management of severe manifestations of influenza,
• initiation of oseltamivir,
• clinical evidence of lower respiratory tract infection (e.g. shortness of breath, tachypnea, oxygen desaturation <93% on room air, crepitations on auscultation, infiltrations or consolidations on chest radiograph)
• written informed consent (by the subjects, or from their next of kin if the subjects are unable to provide written consent at the time of enrollment)

Exclusion criteria

• use of immunosuppressants (e.g. post-chemotherapy, post-transplant, autoimmune diseases) other than systemic corticosteroids
• known immuno-compromised conditions (e.g. active haematological malignancies, HIV/AIDS patients who are on antiretroviral therapy and CD4 cell count < 200),
• pregnancy
• lactation,
• end-stage renal failure
• hepatic failure
• cardiac failure
• patients on anticoagulation (except prophylactic dose of low molecular weight heparin),
• patients with scheduled major surgery within 2 weeks (NAC may affect blood clotting),
• patients who have received macrolide antibiotics and NSAID for 1 week prior to enrolment due to their immuno-modulating effects.
• Use of investigational anti-influenza antivirals and blood products

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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160 participants in 2 patient groups, including a placebo group

intravenous N-acetylcysteine (NAC) and oseltamivir

Active Comparator group

Treatment:

Drug: N-acetyl cysteine

intravenous 5% dextrose and oseltamivir

Placebo Comparator group

Treatment:

Drug: 5% Dextrose