InfluenzaPhase 3NCT03901001
Adjunctive Sirolimus and Oseltamivir Versus Oseltamivir Alone for Treatment of Influenza
A Phase 3 study testing sirolimus and oseltamivir and Oseltamivir in people with Influenza, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
Seasonal influenza epidemics are important causes of mortality and morbidity. Cytokine dysregulation, with high levels of pro-inflammatory cytokines, occurs in patients with severe influenza A(H1N1)pdm09 virus infection, A(H5N1) infection, and A(H7N9) infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Influenza
- What is being tested?
- sirolimus and oseltamivir and Oseltamivir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteHong Kong
- Study dates
- 8 May 2023to 31 Dec 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- influenza A and B virus infections confirmed by 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, crepitations on auscultation, infiltrations or consolidations on chest radiograph) and 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)
Who cannot join
- use of other immunosuppressants (e.g. post-chemotherapy, post-transplant, autoimmune diseases) other than systemic corticosteroids
- patients with known immuno-compromised conditions (e.g. active haematological malignancies, HIV/AIDS patients who are on antiretroviral therapy and CD4 cell count < 200)
- pregnancy/lactation
- hepatic failure
- patients with surgery done/planned within 1 month
- patients who have received macrolide antibiotics and NSAID for 1 week prior to enrolment due to their immuno-modulating effects
- patients on drugs that may interact and alter sirolimus level (rifampicin, azole antifungals, phenytoin, diltiazem, verapamil, nicardipine, metoclopramide, phenobarbital, carbamazepine) will be excluded for safety purposes
- Use of investigational anti-influenza antivirals and blood products
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Controlled Trial of Adjunctive Sirolimus and Oseltamivir Versus Oseltamivir Alone for Treatment of Influenza
Seasonal influenza epidemics are important causes of mortality and morbidity. Cytokine dysregulation, with high levels of pro-inflammatory cytokines, occurs in patients with severe influenza A(H1N1)pdm09 virus infection, A(H5N1) infection, and A(H7N9) infection. We aim to investigate the effects of adjunctive sirolimus in adults hospitalized with influenza A or B infections involving the lower respiratory tract.
Read the detailed description
The investigators aim to investigate the effects of adjunctive sirolimus in adults hospitalized with influenza A or B infections involving the lower respiratory tract. Patients will be randomized to either oseltamivir and adjunctive sirolimus or oseltamivir alone and assessed with reference to normalization of respiratory status (SaO2 ≥93% or respiratory rate ≤20/min on room air) as the primary endpoint,10 cytokines/chemokines and pro-inflammatory mediator changes, viral clearance, symptom resolution, ICU admission/death, day 28 mortality; safety profiles will also be assessed.
The investigators hypothesize that addition of sirolimus to oseltamivir would improve respiratory status and other endpoints more effectively than oseltamivir alone through reduction of inflammatory responses without affecting viral clearance.
- Conditions
- Influenza
- Being tested
- sirolimus and oseltamivir, Oseltamivir
- Keywords
- respiratory, Mortality, cytokines, chemokines
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimus and oseltamivirDrug
Sirolimus 1 mg daily and oseltamivir 75 mg bid for 5 days, both given orally. Extension of dosing to 10 days for oseltamivir and the study drug is allowed if there is slow recovery, lack of improvement, or deterioration.
OseltamivirDrug
oral oseltamivir 75 mg bid alone 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.
| Study group | Role | What they receive |
|---|---|---|
| oseltamivir and adjunctive sirolimus | Active comparator | Sirolimus 1 mg daily and oseltamivir 75 mg bid for 5 days, both given orally. Extension of dosing to 10 days for oseltamivir and the study drug is allowed if there is slow recovery, lack of improvement, or deterioration. Receives: Drug: sirolimus and oseltamivir |
| oseltamivir alone | Placebo comparator | oral oseltamivir 75 mg bid alone 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. Receives: Drug: Oseltamivir |
What is being measured
The primary outcome is the main question the study is designed to answer.
normalisation of respiratory status
SaO2 ≥93% or respiratory rate ≤20/min on room air
Measured: 28 days
Secondary outcomes (14)
viral ribonucleic acid (RNA) in copies per milliliter
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')
Measured: 28 days
Interleukin 6 in pg/ml
Measured: 10 days
interleukin-8 in pg/ml
Measured: 10 days
interleukin 17 in pg/ml
Measured: 10 days
Chemokine ligand 9 (CxCL9/MIG) in pg/ml
Measured: 10 days
Soluble tumour necrosis factor receptor-1 (sTNFR-1) in pg/ml
Measured: 10 days
interleukin 18 in pg/ml
Measured: 10 days
CRP in mg/L
Measured: 10 days
phospho-p38 and phospho-ERK (activated MAPKs) in mean fluorescence intensity(MFI)
Measured: 10 days
phospho-inhibitor kB/IkB (NF-kB) in mean fluorescence intensity(MFI)
Measured: 10 days
resolution of symptoms in 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.
Measured: 28 days
ICU admission in days
Measured: 28 days
mortality in days
Measured: 28 days
Incidence of Treatment-Emergent Adverse Events in numbers
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2019
- Study start8 May 2023
- Primary completion16 May 2026
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized trial into either oseltamivir and adjunctive sirolimus or oseltamivir alone
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof David Shu Cheong Hui, Chinese University of Hong Kong
- Investigators
- David SC Hui, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03901001
- Sponsor's protocol ID
- Sirolimus influenza/Hui/2019
- Status last verified
- Oct 2026
- First submitted
- 30 Mar 2019
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No