A Study of Intravenous Zanamivir Versus Oral Oseltamivir in Adults and Adolescents Hospitalized With Influenza
ZORO
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
1 other identifier
interventional
626
28 countries
170
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jan 2011
Typical duration for phase_3
170 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 28, 2010
CompletedFirst Posted
Study publicly available on registry
November 1, 2010
CompletedStudy Start
First participant enrolled
January 15, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 18, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
March 18, 2015
CompletedResults Posted
Study results publicly available
November 20, 2017
CompletedOctober 15, 2018
March 1, 2018
4.2 years
October 28, 2010
April 11, 2017
September 14, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Time to Clinical Response (TTCR) in Participants With Confirmed Influenza
Clinical response is defined as the resolution of at least 4 of the 5 vital signs (temperature, oxygen saturation, respiratory status, heart rate, systolic blood pressure) within the respective resolution criteria, maintained for at least 24 hours, or hospital discharge, whichever occurred first. This analysis was performed for Influenza positive population, for those with symptom onset less than or equal to (\<=) 4 days, and for those on mechanical (mech) ventilation or in intensive care unit (ICU). 99 days is censored time for the participants who did not achieve TTCR.
Up to 42 days
Secondary Outcomes (31)
Percentage of Participants With Respiratory Improvement
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
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
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
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
Up to 42 days
- +26 more secondary outcomes
Study Arms (3)
Intravenous (IV) Zanamivir 300mg Twice Daily
EXPERIMENTAL300mg of IV zanamivir infusion twice daily plus oral oseltamivir placebo twice daily
Intravenous (IV) Zanamivir 600mg Twice Daily
EXPERIMENTAL600mg of IV zanamivir infusion twice daily plus oral oseltamivir placebo twice daily
Oral Oseltamivir 75mg Twice Daily
ACTIVE COMPARATOR75mg oral oseltamivir twice daily plus intravenous placebo zanamivir twice daily
Interventions
Zanamivir aqueous solution, 10 mg/mL, will be provided as a single use, sterile clear, colorless preparation in 20 mL clear glass vials.
Placebo to match IV zanamivir will be provided as a normal saline solution of a matched volume.
Oseltamivir will be provided as over-encapsulated 75 mg capsules.
Placebo to match oral oseltamivir will be provided as capsules with a common excipient of appropriate quality.
Eligibility Criteria
You may qualify if:
- Male or female aged 16 years; a female is eligible to enter and participate in the study if she is:
- of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post- menopausal); or,
- 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:
- 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:
- 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.
- Respiration rate \>24 breaths per minute. For those subjects who require ventilatory support or oxygen supplementation, this requirement is waived.
- Heart rate \>100 beats per minute.
- 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
You may not qualify if:
- 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:
- ALT or AST 3xULN and bilirubin 2xULN
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (170)
GSK Investigational Site
Birmingham, Alabama, 35249, United States
GSK Investigational Site
Phoenix, Arizona, 85023, United States
GSK Investigational Site
Chula Vista, California, 91911, United States
GSK Investigational Site
Escondido, California, 92025, United States
GSK Investigational Site
Fullerton, California, 92835, United States
GSK Investigational Site
La Jolla, California, 92037, United States
GSK Investigational Site
La Mesa, California, 91942, United States
GSK Investigational Site
Oceanside, California, 92056, United States
GSK Investigational Site
Aurora, Colorado, 80045, United States
GSK Investigational Site
Stamford, Connecticut, 06902, United States
GSK Investigational Site
Orlando, Florida, 32806, United States
GSK Investigational Site
Sarasota, Florida, 34239, United States
GSK Investigational Site
Sunrise, Florida, 33323, United States
GSK Investigational Site
Atlanta, Georgia, 30342, United States
GSK Investigational Site
Augusta, Georgia, 30912, United States
GSK Investigational Site
Idaho Falls, Idaho, 83404, United States
GSK Investigational Site
Chicago, Illinois, 60611, United States
GSK Investigational Site
Oak Park, Illinois, 60302, United States
GSK Investigational Site
Peoria, Illinois, 61637, United States
GSK Investigational Site
Council Bluffs, Iowa, 51503, United States
GSK Investigational Site
Topeka, Kansas, 66604, United States
GSK Investigational Site
Louisville, Kentucky, 40241, United States
GSK Investigational Site
Boston, Massachusetts, 02115, United States
GSK Investigational Site
Royal Oak, Michigan, 48073, United States
GSK Investigational Site
Troy, Michigan, 48085, United States
GSK Investigational Site
St Louis, Missouri, 63110-1093, United States
GSK Investigational Site
Missoula, Montana, 59802, United States
GSK Investigational Site
Las Vegas, Nevada, 89109, United States
GSK Investigational Site
Valhalla, New York, 10595, United States
GSK Investigational Site
Asheville, North Carolina, 28801, United States
GSK Investigational Site
Chapel Hill, North Carolina, 27599-7215, United States
GSK Investigational Site
Bismarck, North Dakota, 58504, United States
GSK Investigational Site
Cleveland, Ohio, 44195, United States
GSK Investigational Site
Columbus, Ohio, 43215, United States
GSK Investigational Site
Toledo, Ohio, 43608, United States
GSK Investigational Site
Bethlehem, Pennsylvania, 18105, United States
GSK Investigational Site
Philadelphia, Pennsylvania, 19107, United States
GSK Investigational Site
Houston, Texas, 77030, United States
GSK Investigational Site
Roanoke, Virginia, 24013, United States
GSK Investigational Site
Marshfield, Wisconsin, 54449, United States
GSK Investigational Site
Westmead, New South Wales, 2145, Australia
GSK Investigational Site
Herston, Queensland, 4029, Australia
GSK Investigational Site
Adelaide, South Australia, 5000, Australia
GSK Investigational Site
Bedford Park, South Australia, 5043, Australia
GSK Investigational Site
Clayton, Victoria, 3168, Australia
GSK Investigational Site
Heidelberg, Victoria, 3084, Australia
GSK Investigational Site
Melbourne, Victoria, 3004, Australia
GSK Investigational Site
Melbourne, Victoria, 3050, Australia
GSK Investigational Site
Perth, Western Australia, 6000, Australia
GSK Investigational Site
Brussels, 1070, Belgium
GSK Investigational Site
Brussels, 1090, Belgium
GSK Investigational Site
Leuven, 3000, Belgium
GSK Investigational Site
Liège, 4000, Belgium
GSK Investigational Site
Rio de Janeiro, 21040-900, Brazil
GSK Investigational Site
SĂ£o Paulo, 01308-050, Brazil
GSK Investigational Site
Calgary, Alberta, T1Y 6J4, Canada
GSK Investigational Site
Calgary, Alberta, T2N 2T9, Canada
GSK Investigational Site
Halifax, Nova Scotia, B3H 3A7, Canada
GSK Investigational Site
Hamilton, Ontario, L8N 4A6, Canada
GSK Investigational Site
Toronto, Ontario, M5G 2C4, Canada
GSK Investigational Site
Chicoutimi, Quebec, G7H 5H6, Canada
GSK Investigational Site
Montreal, Quebec, H1T 2M4, Canada
GSK Investigational Site
Montreal, Quebec, H2W1T8, Canada
GSK Investigational Site
Trois-Rivières, Quebec, G8Z 3R9, Canada
GSK Investigational Site
Haikou, Hainan, 570311, China
GSK Investigational Site
Changsha, Hunan, 410005, China
GSK Investigational Site
Nanchang, Jiangxi, 330006, China
GSK Investigational Site
Changchun, Jilin, 130041, China
GSK Investigational Site
Xi'an, Shaanxi, 710032, China
GSK Investigational Site
Hangzhou, Zhejiang, 310003, China
GSK Investigational Site
Beijing, 100015, China
GSK Investigational Site
Beijing, 100044, China
GSK Investigational Site
Chengdu, 610041, China
GSK Investigational Site
Chongqing, 400016, China
GSK Investigational Site
Guangzhou, 510120, China
GSK Investigational Site
Hangzhou, 310016, China
GSK Investigational Site
Shanghai, 200025, China
GSK Investigational Site
Tianjin, 300052, China
GSK Investigational Site
BogotĂ¡, Colombia
GSK Investigational Site
Brno, 625 00, Czechia
GSK Investigational Site
Brno-Bohunice, 625 00, Czechia
GSK Investigational Site
Hradec KrĂ¡lovĂ©, 500 05, Czechia
GSK Investigational Site
Prague, 180 01, Czechia
GSK Investigational Site
Aarhus N, 8200, Denmark
GSK Investigational Site
Hvidovre, DK-2650, Denmark
GSK Investigational Site
Odense C, 5000, Denmark
GSK Investigational Site
Dijon, 21079, France
GSK Investigational Site
Limoges, 87042, France
GSK Investigational Site
Nîmes, 30029, France
GSK Investigational Site
Orléans, 45067, France
GSK Investigational Site
Poitiers, 86021, France
GSK Investigational Site
Tours, 37044, France
GSK Investigational Site
Ulm, Baden-Wurttemberg, 89081, Germany
GSK Investigational Site
Erlangen, Bavaria, 91054, Germany
GSK Investigational Site
Regensburg, Bavaria, 93053, Germany
GSK Investigational Site
Hanover, Lower Saxony, 30625, Germany
GSK Investigational Site
Homburg, Saarland, 66421, Germany
GSK Investigational Site
ChaĂ¯dĂ¡ri, 12462, Greece
GSK Investigational Site
Goudi, Athens, 11527, Greece
GSK Investigational Site
Kwun Tong, Hong Kong
GSK Investigational Site
Shatin, Hong Kong
GSK Investigational Site
Tuenmen, Hong Kong
GSK Investigational Site
Debrecen, 4031, Hungary
GSK Investigational Site
KaposvĂ¡r, 7400, Hungary
GSK Investigational Site
Miskolc, 3529, Hungary
GSK Investigational Site
SzĂ©kesfehĂ©rvĂ¡r, 8000, Hungary
GSK Investigational Site
Szombathely, 9700, Hungary
GSK Investigational Site
Bangalore, 560010, India
GSK Investigational Site
Civil Lines, 141001, India
GSK Investigational Site
Lucknow, 226003, India
GSK Investigational Site
Lucknow, 226005, India
GSK Investigational Site
Pune, 411004, India
GSK Investigational Site
Pune, 411018, India
GSK Investigational Site
Trivandrum, 695029, India
GSK Investigational Site
Guadalajara, Jalisco, 44280, Mexico
GSK Investigational Site
San NicolĂ¡s de los Garza, Nuevo LeĂ³n, 66480, Mexico
GSK Investigational Site
CuautitlĂ¡n, Estado de MĂ©xico, State of Mexico, 54800, Mexico
GSK Investigational Site
Aguascalientes, 20230, Mexico
GSK Investigational Site
Chihuahua City, 31238, Mexico
GSK Investigational Site
Nijmegen, 6500 HB, Netherlands
GSK Investigational Site
Auckland, 1001, New Zealand
GSK Investigational Site
Auckland, 1701, New Zealand
GSK Investigational Site
Auckland, New Zealand
GSK Investigational Site
Christchurch, 8001, New Zealand
GSK Investigational Site
Hamilton, 3204, New Zealand
GSK Investigational Site
Hastings, 4120, New Zealand
GSK Investigational Site
Newtown, New Zealand
GSK Investigational Site
Bergen, 5053, Norway
GSK Investigational Site
Trondheim, 7030, Norway
GSK Investigational Site
ChorzĂ³w, 41-500, Poland
GSK Investigational Site
Dębica, 39-200, Poland
GSK Investigational Site
Trzebnica, 55-100, Poland
GSK Investigational Site
Warsaw, 01-201, Poland
GSK Investigational Site
Barnaul, 656024, Russia
GSK Investigational Site
Barnaul, 656038, Russia
GSK Investigational Site
Saint Petersburg, 191167, Russia
GSK Investigational Site
Saint Petersburg, 197022, Russia
GSK Investigational Site
Smolensk, 214006, Russia
GSK Investigational Site
Bratislava, 833 05, Slovakia
GSK Investigational Site
Martin, 036 59, Slovakia
GSK Investigational Site
Middelburg, Mpumalanga, 1055, South Africa
GSK Investigational Site
Bellville, 7530, South Africa
GSK Investigational Site
Die Wilgers, 0041, South Africa
GSK Investigational Site
Les Marais, 0084, South Africa
GSK Investigational Site
Panorama, 7500, South Africa
GSK Investigational Site
Worcester, 6850, South Africa
GSK Investigational Site
Guro Gu, 152703, South Korea
GSK Investigational Site
Gyeonggi-do, 442-723, South Korea
GSK Investigational Site
Kangwon-do, 220-701, South Korea
GSK Investigational Site
Seoul, 150-030, South Korea
GSK Investigational Site
Seoul, 150-950, South Korea
GSK Investigational Site
Alicante, 03010, Spain
GSK Investigational Site
Badalona, 08916, Spain
GSK Investigational Site
Barcelona, 08003, Spain
GSK Investigational Site
Granada, 18012, Spain
GSK Investigational Site
Granada, 18014, Spain
GSK Investigational Site
L'Hospitalet de Llobregat, 08907, Spain
GSK Investigational Site
Madrid, 28007, Spain
GSK Investigational Site
Madrid, 28040, Spain
GSK Investigational Site
Madrid, 28046, Spain
GSK Investigational Site
Murcia, 30003, Spain
GSK Investigational Site
Oviedo, 33006, Spain
GSK Investigational Site
Pama de Mallorca, 07010, Spain
GSK Investigational Site
Taipei, 112, Taiwan
GSK Investigational Site
Bangkok, 10400, Thailand
GSK Investigational Site
Bangkok, 10700, Thailand
GSK Investigational Site
Bristol, BS2 8HW, United Kingdom
GSK Investigational Site
Cardiff, CF14 4XW, United Kingdom
GSK Investigational Site
Liverpool, L7 8XP, United Kingdom
GSK Investigational Site
Manchester, M13 9WL, United Kingdom
Related Publications (2)
van Duijnhoven W, Van Dromme I, Haesendonckx S, Witek J, Leopold L. The Hospital Recovery Scale: A clinically useful endpoint in patients hospitalized with influenza. Contemp Clin Trials. 2022 Dec;123:106952. doi: 10.1016/j.cct.2022.106952. Epub 2022 Oct 3.
PMID: 36202198DERIVEDMarty FM, Vidal-Puigserver J, Clark C, Gupta SK, Merino E, Garot D, Chapman MJ, Jacobs F, Rodriguez-Noriega E, Husa P, Shortino D, Watson HA, Yates PJ, Peppercorn AF. Intravenous zanamivir or oral oseltamivir for hospitalised patients with influenza: an international, randomised, double-blind, double-dummy, phase 3 trial. Lancet Respir Med. 2017 Feb;5(2):135-146. doi: 10.1016/S2213-2600(16)30435-0. Epub 2017 Jan 14.
PMID: 28094141DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 28, 2010
First Posted
November 1, 2010
Study Start
January 15, 2011
Primary Completion
March 18, 2015
Study Completion
March 18, 2015
Last Updated
October 15, 2018
Results First Posted
November 20, 2017
Record last verified: 2018-03
Data Sharing
- IPD Sharing
- Will share
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.