Intravenous N-acetylcysteine and Oseltamivir Versus Oseltamivir in Adults Hospitalized With Influenza and Pneumonia
- Registration Number
- NCT03900988
- Lead Sponsor
- Chinese University of Hong Kong
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 160
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description intravenous N-acetylcysteine (NAC) and oseltamivir N-acetyl cysteine - intravenous 5% dextrose and oseltamivir 5% Dextrose -
- Primary Outcome Measures
Name Time Method Normalization of respiratory status in day 28 days oxygen saturation more than 93% or respiratory rate lower than 20/min on room air
- Secondary Outcome Measures
Name Time Method CRP in mg/L 10 days interleukin 18 in pg/ml 10 days phospho-p38 and phospho-ERK (activated MAPKs) in mean fluorescence intensity(MFI) 10 days interleukin-8 in pg/ml 10 days Chemokine ligand 9 (CxCL9/MIG) in pg/ml 10 days phospho-inhibitor kB/IkB (NF-kB) in mean fluorescence intensity(MFI) 10 days mortality in days 28 days viral ribonucleic acid (RNA) in copies per milliliter 28 days All serially collected samples will be subjected to viral ribonucleic acid (RNA) quantification using quantitative reverse transcription PCR (qRTPCR) targeting the matrix (M)-gene ('viral load')
Interleukin 6 in pg/ml 10 days interleukin 17 in pg/ml 10 days ICU admission in days 28 days a six step ordinal scale of clinical status 7 days death, in ICU, ongoing hospitalisation on oxygen, hospital stay not on oxygen, discharged but not returned to normal activities, or discharged and returned to normal activities
Soluble tumour necrosis factor receptor-1 (sTNFR-1) in pg/ml 10 days resolution of symptoms in days 28 days A standard questionnaire will be used to collect baseline and serial clinical data. These include clinical manifestations/complications, symptom severity score, vital signs (e.g. temperature, respiratory rate, oxygen saturation), fever duration, requirements for supplemental oxygen therapy and invasive/non-invasive ventilation, duration of hospitalization, death, and occurrence of adverse events.
Incidence of Treatment-Emergent Adverse Events in numbers 28 days
Trial Locations
- Locations (1)
Prince of Wales Hospital
ðŸ‡ðŸ‡°Hong Kong, Hong Kong