Trial Outcomes & Findings for High-Dose Versus Standard-Dose Oseltamivir to Treat Severe Influenza and Avian Influenza (NCT NCT00298233)

NCT ID: NCT00298233

Last Updated: 2014-06-06

Results Overview

Proportion of all participants with no detectable viral RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in a combined nasal and throat swab sample on day 5.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 326 participants
• Primary outcome timeframe: After 5 days of treatment
• Results posted on: 2014-06-06

Participant Flow

Participant milestones

Measure	Standard Dose Oseltamivir Adult Cohort All participants \>= 15 years received standard-dose oseltamivir (75 mg twice daily orally or equivalent dose adjusted for age, weight, and kidney function) for 5 to 10 days.	Double Dose Oseltamivir Adult Cohort All Participants \>= 15 years received high-dose oseltamivir (150 mg twice daily orally or equivalent dose adjusted for age, weight, and kidney function) for 5 to 10 days.	Standard Dose Oseltamivir Child Cohort All participants \<15 years received standard dose oseltamivir (75 mg twice daily orally or equivalent dose adjusted for age, weight, and kidney function) for 5 to 10 days.	Double Dose Oseltamivir Child Cohort All Participants \<15 years received high-dose oseltamivir (150 mg twice daily orally or equivalent dose adjusted for age, weight, and kidney function) for 5 to 10 days.
Overall Study STARTED	39	41	122	124
Overall Study COMPLETED	39	41	122	124
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

High-Dose Versus Standard-Dose Oseltamivir to Treat Severe Influenza and Avian Influenza

Baseline characteristics by cohort

Measure	Standarad Dose Oseltamivir n=161 Participants All participants that were randomized and received standard dose oseltamivir	Double Dose Oseltamivir n=165 Participants All participants that were randomized and received doubledose oseltamivir	Total n=326 Participants Total of all reporting groups
Age, Customized Child cohort: ≥1 to <15 years	122 participants n=5 Participants	124 participants n=7 Participants	246 participants n=5 Participants
Age, Customized Adult cohort: ≥15 years	39 participants n=5 Participants	41 participants n=7 Participants	80 participants n=5 Participants
Sex: Female, Male Female	72 Participants n=5 Participants	69 Participants n=7 Participants	141 Participants n=5 Participants
Sex: Female, Male Male	89 Participants n=5 Participants	96 Participants n=7 Participants	185 Participants n=5 Participants

PRIMARY outcome

Timeframe: After 5 days of treatment

Population: All randomized patients with RT-PCR proven influenza.

Proportion of all participants with no detectable viral RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in a combined nasal and throat swab sample on day 5.

Outcome measures

Measure	Double Dose Oseltamivir n=159 Participants All participants receiving double dose oseltamivir	Standard Dose Oseltamivir n=154 Participants All participants receiving standard dose oseltamivir
Proportion of All Participants Negative for Viral RNA on Day 5	115 participants	105 participants

SECONDARY outcome

Timeframe: After 5 days of treatment

Population: For the purpose of endpoint definition, death prior to or on Day 5 was also considered as clinical failure on day 5.In the double dose cohort, only 154 subjects completed fives days of drug and 7 died (total 161). In the standard dose cohort only 149 subjects completed 5 days of drug and 9 died (total 158).

Proportion of participants that have clinical failure by day 5. Subjects that meet one of the following on Day 5 will be classified as a clinical failure:

• Severe tachypnea (respiratory rate ≥ 30 for ages ≥12 years, rate ≥ 40 for ages 6 to 12 years, rate ≥45 for ages 3 to 6 years, rate ≥ 50 for ages 1 to 3 years)
• Severe dyspnea (unable to speak full sentences, or use of accessory respiratory muscles)
• Arterial oxygen saturation ≤92% on room air by trans-cutaneous method
• Need for mechanical ventilation or intensive care unit (ICU) admission For the purpose of endpoint definition, death prior to or on Day 5 will also be considered a clinical failure at Day 5.

Outcome measures

Measure	Double Dose Oseltamivir n=161 Participants All participants receiving double dose oseltamivir	Standard Dose Oseltamivir n=158 Participants All participants receiving standard dose oseltamivir
Participants Meeting Criteria for Day 5 Clinical Failure	16 participants	20 participants

SECONDARY outcome

Timeframe: After up to 10 days of treatment

Standard therapy with oseltamivir is five days. Those patients with persistent symptoms on day five were continued on the randomized dose for an additional five days and assessments were performed up to day 10.

Outcome measures

Measure	Double Dose Oseltamivir n=165 Participants All participants receiving double dose oseltamivir	Standard Dose Oseltamivir n=161 Participants All participants receiving standard dose oseltamivir
In-hospital Mortality Rates	12 participants	9 participants

SECONDARY outcome

Timeframe: Throughout study, 14 days

Outcome measures

Measure	Double Dose Oseltamivir n=165 Participants All participants receiving double dose oseltamivir	Standard Dose Oseltamivir n=161 Participants All participants receiving standard dose oseltamivir
Median Time (Days) Receipt of Oxygen	3 days 95% Confidence Interval 2-5 • Interval 2.0 to 5.0	3.5 days 95% Confidence Interval 2-7 • Interval 2.0 to 7.0

SECONDARY outcome

Timeframe: Throughout study, 14 days

Outcome measures

Measure	Double Dose Oseltamivir n=165 Participants All participants receiving double dose oseltamivir	Standard Dose Oseltamivir n=161 Participants All participants receiving standard dose oseltamivir
Median Time (Days) in ICU	4.4 days Interval 3.0 to 6.0	5 days Interval 2.0 to 11.0

SECONDARY outcome

Timeframe: Throughout study, 14 days

Use of mechanical ventilation at any time for subjects with severe influenza and avian influenza.

Outcome measures

Measure	Double Dose Oseltamivir n=165 Participants All participants receiving double dose oseltamivir	Standard Dose Oseltamivir n=161 Participants All participants receiving standard dose oseltamivir
Median Time (Days) on Ventilation	2.5 days Interval 1.0 to 16.0	5 days Interval 2.0 to 11.0

Adverse Events

Double Dose Oseltamivir

Serious events: 1 serious events

Other events: 37 other events

Deaths: 0 deaths

Standard Dose Oseltamivir

Serious events: 0 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Measure	Double Dose Oseltamivir n=165 participants at risk The study recorded only cumulative data (total number of adverse events (AEs) per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	Standard Dose Oseltamivir n=161 participants at risk The study recorded only cumulative data (total number of adverse events (AEs) per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.
Respiratory, thoracic and mediastinal disorders Septic shock	0.61% 1/165 • Number of events 1 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	0.00% 0/161 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.

Other adverse events

Measure	Double Dose Oseltamivir n=165 participants at risk The study recorded only cumulative data (total number of adverse events (AEs) per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	Standard Dose Oseltamivir n=161 participants at risk The study recorded only cumulative data (total number of adverse events (AEs) per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.
Respiratory, thoracic and mediastinal disorders respiratory failure	6.1% 10/165 • Number of events 10 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	3.1% 5/161 • Number of events 5 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.
Gastrointestinal disorders diarrhea	1.2% 2/165 • Number of events 2 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	5.6% 9/161 • Number of events 9 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.
General disorders multi-organ failures	1.8% 3/165 • Number of events 3 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	1.9% 3/161 • Number of events 3 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.
Respiratory, thoracic and mediastinal disorders acute respiratory distress syndrome	1.2% 2/165 • Number of events 2 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	0.62% 1/161 • Number of events 1 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.
Respiratory, thoracic and mediastinal disorders pneumothorax	0.61% 1/165 • Number of events 1 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	1.2% 2/161 • Number of events 2 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.
Blood and lymphatic system disorders neutropenia	1.2% 2/165 • Number of events 2 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	0.62% 1/161 • Number of events 1 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.
Blood and lymphatic system disorders Thrombocytosis	1.8% 3/165 • Number of events 3 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	0.00% 0/161 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.
General disorders Pyrexia	0.61% 1/165 • Number of events 1 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	0.62% 1/161 • Number of events 1 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.
Respiratory, thoracic and mediastinal disorders Bronchitis	0.00% 0/165 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	1.2% 2/161 • Number of events 2 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.
Cardiac disorders Septic shock	0.61% 1/165 • Number of events 1 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	1.2% 2/161 • Number of events 2 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.
Skin and subcutaneous tissue disorders Rash	1.2% 2/165 • Number of events 2 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	0.62% 1/161 • Number of events 1 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.
General disorders other	6.1% 10/165 • Number of events 10 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.	6.8% 11/161 • Number of events 11 • Through Day 28 for severe influenza, and Day 180 for avian influenza. The study recorded only cumulative data (total number of AEs per type, per Arm, but not number of subjects affected per AE type). Therefore data are the number of events and not the number of participants with events.

Additional Information

Dr. Jeremy Farrar

Oxford University Clinical Research Unit

Phone: +84 839237954

Email: info@oucru.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place