Last updated: 11/07/2018 07:39:21
A Study of Intravenous Zanamivir versus Oral Oseltamivir in Adults and Adolescents Hospitalized with InfluenzaZORO
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Phase III international, randomized, double-blind, double-dummy study to evaluate the efficacy and safety of 300 mg or 600 mg of intravenous zanamivir twice daily compared to 75 mg of oral oseltamivir twice daily in the treatment of hospitalized adults and adolescents with influenza
Trial description: The purpose of this study is to test the safety and efficacy of zanamivir given intravenously and how well it works at two different doses in hospitalized adolescents and adults with flu. Zanamivir will be compared with oseltamivir, which is used for treating flu.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Time to clinical response (TTCR) in participants with confirmed influenza
Timeframe: Up to 42 days
Secondary outcomes:
Percentage of participants with respiratory improvement
Timeframe: Up to 42 days
Number of participants with all cause and attributable mortality at Day 14, at Day 28, and at the End of Study Visit
Timeframe: On or before Day 14, Day 28, End of Study Visit (assessed up to 42 days)
Change from Baseline in the Katz Activities of Daily Living (ADL) score and each ADL activity score
Timeframe: Baseline (Day 1) and up to 42 days
Median time to return to pre-morbid functional status as measured by the Katz ADL score and each ADL activity score
Timeframe: Up to 42 days
Number of participants who returned to their pre-morbid functional status as assessed per the Katz ADL score and each ADL activity score at the end of the study
Timeframe: Up to 42 days
Median time to return to the pre-morbid level of activity as measured by the 3-point scale
Timeframe: Up to 42 days
Number of participants with the indicated clinical symptoms of influenza
Timeframe: Up to 42 days
Median time of duration of clinical symptoms of influenza
Timeframe: Up to 42 days
Number of participants with complications of influenza and associated antibiotic use
Timeframe: Up to 42 days
Number of participants with the indicated ventilation status: modality of invasive and non-invasive ventilator support and oxygen supplementation
Timeframe: Up to 42 days
Median time of duration of invasive and non-invasive ventilator support and oxygen supplementation
Timeframe: Baseline (Day 1) and up to 42 days
Median time of duration of hospitalization and Intensive Care Unit (ICU) stay
Timeframe: Day 1 to the end of the study (assessed up to 42 days)
Median time to the absence of fever and improved respiratory status, oxygen saturation, heart rate, and systolic blood pressure
Timeframe: Baseline (Day 1) and up to 42 days
Median time to virologic improvement
Timeframe: Baseline (Day 1) and up to 42 days
Change from Baseline in quantitative virus culture from nasopharyngeal swabs positive at Baseline
Timeframe: Baseline (Day 1), Day 3, Day 5, Day 8, Day 10, Day 11 and/or last day of randomized treatment, if randomized treatment was extended beyond 5 days, and S/R Day 5/6 (up to Day 14) if applicable
Change from Baseline viral load (influenza A or B) by qPCR from nasopharyngeal swabs positive at Baseline
Timeframe: Baseline (Day 1), Day 3, Day 5, Day 8, Day 10, Day 11 and/or last day of randomized treatment, if randomized treatment was extended beyond 5 days, and S/R Day 5/6 (up to Day 14) if applicable
Number of participants with no detectable viral RNA and the absence of cultivable virus in lower respiratory samples (bronchoalveolar lavage sample [BAL], endotracheal aspirate)
Timeframe: Baseline (Day 1) and up to 42 days
Median time to no detectable viral RNA and the absence of cultivable virus in any obtained sample (upper and lower respiratory samples)
Timeframe: Baseline (Day 1) and up to 42 days
Number of participants with resistance-associated mutations detected in the neuraminidase (NA) and hemagglutinin (HA) gene of influenza A and B viruses in nasopharyngeal swabs and endotracheal/BAL samples
Timeframe: Baseline (Day 1) and up to 42 days
Number of participants with any adverse event (AE) considered to be related to study treatment
Timeframe: Up to 42 days
Number of participants with any severe or Grade 3/4 AE
Timeframe: Up to 42 days
Number of participants who permanently discontinued the study treatment due to an AE
Timeframe: Up to 42 days
Number of participants who were permanently discontinued from the study due to an AE
Timeframe: Up to 42 days
Number of participants with any severe or Grade 3/4 treatment-related AE
Timeframe: Up to 42 days
Number of participants with the indicated chemistry laboratory values shifts from Baseline (Day 1) and up to 42 days
Timeframe: Baseline (Day 1) and up to 42 days
Number of participants with the indicated hematology values shifts from Baseline (Day 1) and up to 42 days
Timeframe: Baseline (Day 1) and up to 42 days
Number of participants with the indicated treatment-emergent (TE) Grade (G) 3/4 clinical chemistry toxicities
Timeframe: Baseline (Day 1) and up to 42 days
Number of participants with the indicated treatment-emergent (TE) Grade 3/4 hematology toxicities
Timeframe: Baseline (Day 1) and up to 42 days
Median quantity of oxygen delivery measured at Baseline (Day 1) and during the study
Timeframe: Baseline (Day 1) and during the study
Number of participants assessed as normal/abnormal (clinically significant [CS] and not clinically significant [NCS]) for 12-lead electrocardiogram (ECG) at Baseline (Day 1) and Day 4
Timeframe: Baseline (Day 1) and Day 4
Serum concentration of IV zanamivir
Timeframe: Day 1 and Day 4
Interventions:
Enrollment:
626
Primary completion date:
2015-18-03
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Marty F, Vidal J, Clark C, Gupta S, Merino E, Garot D, Chapman M, Jacobs F, Noriega ER, Husa P, Shortino D, Watson H, Yates P, Peppercorn A. Intravenous zanamivir or oral oseltamivir for hospitalised patients with influenza: an international, randomised, double-blind, double-dummy, Phase III trial. Lancet Respir Med. 2017;5:135-46.
Medical condition
Influenza, Human
Product
zanamivir
Collaborators
Not applicable
Study date(s)
January 2011 to March 2015
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
16+ years
Accepts healthy volunteers
No
- Male or female aged 16 years; a female is eligible to enter and participate in the study if she is:
- a. of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post- menopausal); or,
- Subjects who have taken more than a total of 3 days (6 doses) of approved anti-influenza therapy in the period from onset of symptoms and prior to enrolment.
- Subjects who, in the opinion of the investigator, are not likely to survive beyond 48 hours from Baseline.
Inclusion and exclusion criteria
Inclusion criteria:
- Male or female aged 16 years; a female is eligible to enter and participate in the study if she is: a. of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post- menopausal); or, b. of child-bearing potential, has a negative pregnancy test at Baseline, and agrees to use protocol specified methods of birth control while on study.
- Vital signs criteria defined as 3 or more of the following at Baseline: a. Presence of fever [oral temperature of 38°C or equivalent] at Baseline. However, this requirement is waived if the subject has a history of fever within in the 24 hours prior to Baseline; or, if the subject reported symptoms of feverishness at some time during the 48 hours prior to Baseline. AND at least 2 out of the following 4: b. Oxygen saturation <95% on room air by trans-cutaneous method or need for any supplemental oxygenation or ventilatory support, or increase in oxygen supplementation requirement of ≥2 litres for subjects with chronic oxygen dependency. For those subjects with a history of chronic hypoxia (without supplemental oxygen), an oxygen saturation of at least 3% below the patient’s historical baseline oxygen saturation will satisfy this criterion. c. Respiration rate >24 breaths per minute. For those subjects who require ventilatory support or oxygen supplementation, this requirement is waived. d. Heart rate >100 beats per minute. e. Systolic blood pressure <90 mmHg.
- Onset of influenza symptoms within 6 days prior to study enrolment. Symptoms may include cough, dyspnea, sore throat, feverishness, myalgias, headache, nasal symptoms (rhinorrhea, congestion), fatigue, diarrhea, anorexia, nausea and vomiting.
- Clinical symptoms of influenza with positive influenza diagnostic test result or strong suspicion of influenza illness based on clinical symptoms and local surveillance information.
- Subjects willing and able to give written informed consent to participate in the study and to adhere to the procedures stated in the protocol, or legally acceptable representative willing and able to give written informed consent on behalf of the subject for minors, unconscious adults and those incapable of consenting themselves due to their medical condition, or included as permitted by local regulatory authorities, IRB/IECs or local laws.
- Severity of any medical illness that, in the Investigator’s judgement, justifies hospitalization of the subject for treatment and supportive care
- French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Exclusion criteria:
- Subjects who have taken more than a total of 3 days (6 doses) of approved anti-influenza therapy in the period from onset of symptoms and prior to enrolment.
- Subjects who, in the opinion of the investigator, are not likely to survive beyond 48 hours from Baseline.
- Subjects who are considered to require concurrent therapy with another influenza antiviral medication.
- Subjects who are known or suspected to be hypersensitive to any component of the study medications.
- Subjects with creatinine clearance ≤10 mL/min who are not being treated with continuous renal replacement therapy (CRRT).
- Subjects who require Extra Corporeal Membrane Oxygenation (ECMO) at Baseline
- Subjects who require routine/intermittent hemodialysis or continuous peritoneal dialysis (due to inability to provide appropriate dosing schedule for oseltamivir) at Baseline. CRRT modalities are allowed.
- Liver toxicity criteria based on local laboratory results obtained within 24 hours of Baseline: a. ALT or AST 3xULN and bilirubin 2xULN b. ALT 5xULN
- Underlying chronic liver disease with evidence of severe liver impairment.
- History of severe cardiac disease or clinically significant arrhythmia (either on ECG or by history) which, in the opinion of the Investigator, will interfere with the safety of the individual subject.
- Females who are pregnant or are breastfeeding.
- Treatment with investigational parenteral anti-influenza drugs (IV peramivir, IV zanamivir or IV oseltamivir) in the 4 weeks prior to Baseline.
- French and Korean subjects: the French or Korean subject has participated in any study using an investigational drug during the previous 30 days.
Trial location(s)
Location
GSK Investigational Site
Idaho Falls, Idaho, United States, 83404
Status
Terminated/Withdrawn
Location
GSK Investigational Site
LaJolla, California, United States, 92037
Status
Study Complete
Location
GSK Investigational Site
Sunrise, Florida, United States, 33323
Status
Terminated/Withdrawn
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Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2015-18-03
Actual study completion date
2015-18-03
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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