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Trial record 33 of 36 for:    "Viral Infectious Disease" | "Everolimus"

Adjunctive Sirolimus and Oseltamivir Versus Oseltamivir Alone for Treatment of Influenza

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ClinicalTrials.gov Identifier: NCT03901001
Recruitment Status : Not yet recruiting
First Posted : April 3, 2019
Last Update Posted : May 8, 2019
Sponsor:
Information provided by (Responsible Party):
Prof David Shu Cheong Hui, Chinese University of Hong Kong

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.

Condition or disease Intervention/treatment Phase
Influenza Drug: sirolimus and oseltamivir Drug: Oseltamivir Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: randomized trial into either oseltamivir and adjunctive sirolimus or oseltamivir alone
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial of Adjunctive Sirolimus and Oseltamivir Versus Oseltamivir Alone for Treatment of Influenza
Estimated Study Start Date : August 1, 2020
Estimated Primary Completion Date : July 31, 2022
Estimated Study Completion Date : July 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Active Comparator: oseltamivir and adjunctive sirolimus
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
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.

Placebo Comparator: oseltamivir alone
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
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.




Primary Outcome Measures :
  1. normalisation of respiratory status [ Time Frame: 28 days ]
    SaO2 ≥93% or respiratory rate ≤20/min on room air


Secondary Outcome Measures :
  1. viral ribonucleic acid (RNA) in copies per milliliter [ Time Frame: 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')

  2. Interleukin 6 in pg/ml [ Time Frame: 10 days ]
  3. interleukin-8 in pg/ml [ Time Frame: 10 days ]
  4. interleukin 17 in pg/ml [ Time Frame: 10 days ]
  5. Chemokine ligand 9 (CxCL9/MIG) in pg/ml [ Time Frame: 10 days ]
  6. Soluble tumour necrosis factor receptor-1 (sTNFR-1) in pg/ml [ Time Frame: 10 days ]
  7. interleukin 18 in pg/ml [ Time Frame: 10 days ]
  8. CRP in mg/L [ Time Frame: 10 days ]
  9. phospho-p38 and phospho-ERK (activated MAPKs) in mean fluorescence intensity(MFI) [ Time Frame: 10 days ]
  10. phospho-inhibitor kB/IkB (NF-kB) in mean fluorescence intensity(MFI) [ Time Frame: 10 days ]
  11. resolution of symptoms in days [ Time Frame: 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.

  12. ICU admission in days [ Time Frame: 28 days ]
  13. mortality in days [ Time Frame: 28 days ]
  14. Incidence of Treatment-Emergent Adverse Events in numbers [ Time Frame: 28 days ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • influenza A and B virus infections confirmed by PCR and/or immunofluorescence assays, hospitalized for the management of severe manifestations of influenza, presenting within 5 days from illness onset, 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 ability to provide written informed consent.

Exclusion Criteria:

  • use of systemic corticosteroids (except for those who need low dose hydrocortisone 50mg qid for refractory septic shock) or other immunosuppressants (e.g. post-chemotherapy, post-transplant, autoimmune diseases) or with known immuno-compromised conditions (e.g. active haematological malignancies, HIV/AIDS), pregnancy/lactation, end-stage renal failure/hepatic failure/cardiac failure and patients who have received macrolide antibiotics 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 is also excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03901001


Contacts
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Contact: Susanna So-Shan Ng 98075787 drsssng123@yahoo.com.hk

Sponsors and Collaborators
Chinese University of Hong Kong
Investigators
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Principal Investigator: David SC Hui Chinese University of Hong Kong

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Responsible Party: Prof David Shu Cheong Hui, Professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT03901001     History of Changes
Other Study ID Numbers: Sirolimus influenza/Hui/2019
First Posted: April 3, 2019    Key Record Dates
Last Update Posted: May 8, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Prof David Shu Cheong Hui, Chinese University of Hong Kong:
respiratory
Mortality
cytokines
chemokines
Additional relevant MeSH terms:
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RNA Virus Infections
Virus Diseases
Everolimus
Influenza, Human
Orthomyxoviridae Infections
Respiratory Tract Infections
Respiratory Tract Diseases
Sirolimus
Oseltamivir
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action