Adjunctive Sirolimus and Oseltamivir Versus Oseltamivir Alone for Treatment of Influenza

NCT03901001 | Unknown Phase 3 DMC

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

Brief 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. We aim to investigate the effects of adjunctive sirolimus in adults hospitalized with influenza A or B infections involving the lower respiratory tract.

Conditions

Influenza

Keywords

respiratory; Mortality; cytokines; chemokines

Outcome Measures

Primary Outcomes (1)

• normalisation of respiratory status

  SaO2 ≥93% or respiratory rate ≤20/min on room air

  28 days

Secondary Outcomes (14)

• 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)

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.

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.

Drug: Oseltamivir

Interventions

sirolimus and oseltamivir DRUG

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.

oseltamivir and adjunctive sirolimus

Oseltamivir DRUG

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.

oseltamivir alone

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 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)

You may not qualify if:

• 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

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

Sirolimus; Oseltamivir

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Acetamides; Amides; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• David SC Hui

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ken Ka Pang Chan, MBChB

CONTACT

3505 3532; chankapang@cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: randomized trial into either oseltamivir and adjunctive sirolimus or oseltamivir alone

Study Record Dates

• First Submitted: March 30, 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

Locations

HK (1)