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

NCT03900988 | Unknown Phase 3

• 1 other identifier: NAC Influenza/Hui/2019
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

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

Keywords

respiratory, mortality, cytokines, chemokines, N-acetylcysteine (NAC)

Outcome Measures

Primary Outcomes (1)

• Normalization of respiratory status in day

  oxygen saturation more than 93% or respiratory rate lower than 20/min on room air

  28 days

Secondary Outcomes (15)

• viral ribonucleic acid (RNA) in copies per milliliter

  28 days

• Interleukin 6 in pg/ml

  10 days

• interleukin-8 in pg/ml

  10 days

• interleukin 17 in pg/ml

  10 days

• Chemokine ligand 9 (CxCL9/MIG) in pg/ml

  10 days

Study Arms (2)

intravenous N-acetylcysteine (NAC) and oseltamivir

ACTIVE COMPARATOR

Drug: N-acetyl cysteine

intravenous 5% dextrose and oseltamivir

PLACEBO COMPARATOR

Drug: 5% Dextrose

Interventions

N-acetyl cysteine 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 N-acetylcysteine (NAC) and oseltamivir

5% Dextrose 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.

intravenous 5% dextrose and oseltamivir

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Hong Kong, Hong Kong

RECRUITING

MeSH Terms

Conditions

Influenza, Human

Interventions

Acetylcysteine; Glucose

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Hexoses; Monosaccharides; Sugars; Carbohydrates

Study Officials

• David SC Hui, MD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ken Ka Pang Chan, MBChB

CONTACT

852 3505 3532; chankapang@cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 31, 2019
• First Posted: April 3, 2019
• Study Start: May 8, 2023
• Primary Completion: October 31, 2025
• Study Completion: December 31, 2025
• Last Updated: November 27, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)