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

NCT ID: NCT03900988

Last Updated: 2023-11-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-08
• Study Completion Date: 2025-12-31

Brief Summary

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.

Conditions

Influenza

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

intravenous N-acetylcysteine (NAC) and oseltamivir

Group Type: ACTIVE_COMPARATOR

N-acetyl cysteine

Intervention Type: DRUG

N-acetyl cysteine will be administered at 100 mg/kg daily as a continuous IV infusion (in 1000ml of 5% dextrose) over 24 hrs and oseltamivir 75 mg bid orally for 5 days. Extension of dosing to 10 days for oseltamivir and the study drug is allowed if there is slow recovery, lack of improvement, or deterioration.

intravenous 5% dextrose and oseltamivir

Group Type: PLACEBO_COMPARATOR

5% Dextrose

Intervention Type: DRUG

5% dextrose 1 liter given over 24 hrs and oral oseltamivir 75 mg bid for 5 days. Extension of dosing to 10 days for oseltamivir and the study drug is allowed if there is slow recovery, lack of improvement, or deterioration.

Interventions

N-acetyl cysteine

N-acetyl cysteine will be administered at 100 mg/kg daily as a continuous IV infusion (in 1000ml of 5% dextrose) over 24 hrs and oseltamivir 75 mg bid orally for 5 days. Extension of dosing to 10 days for oseltamivir and the study drug is allowed if there is slow recovery, lack of improvement, or deterioration.

Intervention Type: DRUG

5% Dextrose

5% dextrose 1 liter given over 24 hrs and oral oseltamivir 75 mg bid for 5 days. Extension of dosing to 10 days for oseltamivir and the study drug is allowed if there is slow recovery, lack of improvement, or deterioration.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Prof David Shu Cheong Hui

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David SC Hui, MD

Role: PRINCIPAL_INVESTIGATOR

Chinese University of Hong Kong

Locations

Prince of Wales Hospital

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Ken Ka Pang Chan, MBChB

Role: CONTACT

chankapang@cuhk.edu.hk

852 3505 3532

Facility Contacts

Ken Ka Pang Chan

Role: primary

chankapang@cuhk.edu.hk

3505 3532

Other Identifiers

NAC Influenza/Hui/2019

Identifier Type: -

Identifier Source: org_study_id