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Rapid Empiric Treatment With Oseltamivir Study (RETOS) (RETOS)

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ClinicalTrials.gov Identifier: NCT01248715
Recruitment Status : Completed
First Posted : November 25, 2010
Results First Posted : September 6, 2017
Last Update Posted : November 6, 2017
Sponsor:
Collaborator:
Centers for Disease Control and Prevention
Information provided by (Responsible Party):
Julio Ramirez, University of Louisville

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Influenza
Pneumonia
Intervention Drug: oseltamivir
Enrollment 1107
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Oseltamirvir Standard of Care
Hide Arm/Group Description

These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy.

oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability

These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Period Title: Overall Study
Started 556 551
Completed 55 41
Not Completed 501 510
Reason Not Completed
Not influenza positive             501             510
Arm/Group Title Oseltamirvir Standard of Care Total
Hide Arm/Group Description

These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy.

oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability

These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record. Total of all reporting groups
Overall Number of Baseline Participants 55 41 96
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 55 participants 41 participants 96 participants
63
(41.5 to 84.5)
60
(43 to 77)
61.7
(42.1 to 81.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 41 participants 96 participants
Female
23
  41.8%
23
  56.1%
46
  47.9%
Male
32
  58.2%
18
  43.9%
50
  52.1%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 55 participants 41 participants 96 participants
55
 100.0%
41
 100.0%
96
 100.0%
Nursing home Resident  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 41 participants 96 participants
0
   0.0%
2
   4.9%
2
   2.1%
1.Primary Outcome
Title Number of Participants With Clinical Failure (Failure to Reach Clinical Stability)
Hide Description Number of subject that showed lack of clinical improvement within 7 days. Criteria for clinical improvement include no fever; white blood cell count decreases, or increases in the case of leukopenia, to more than 10% from the prior day; the evaluation of signs and symptoms of CAP to define when the patient is subjectively better, and the patient is able to tolerate food by mouth.
Time Frame 7 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oseltamirvir Standard of Care
Hide Arm/Group Description:

These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy.

oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability

These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Overall Number of Participants Analyzed 55 41
Measure Type: Count of Participants
Unit of Measure: Participants
6
  10.9%
2
   4.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oseltamirvir, Standard of Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .460
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Primary Outcome
Title Number of Participants to Transfer to ICU After 24 h
Hide Description Number of subjects that were transfered to an intensive care unit (ICU) after 24 hours of hospitalization. A patient transferred to ICU within 24 hours of admission was considered as a direct admission to ICU and not meeting criteria for clinical failure.
Time Frame 24 h
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oseltamirvir Standard of Care
Hide Arm/Group Description:

These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy.

oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability

These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Overall Number of Participants Analyzed 55 41
Measure Type: Count of Participants
Unit of Measure: Participants
2
   3.6%
2
   4.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oseltamirvir, Standard of Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .9999
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
3.Primary Outcome
Title Number of Participants That Required Re-hospitalization
Hide Description Participants that were re-hospitalized within 30 days after enrollment.
Time Frame 30 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oseltamirvir Standard of Care
Hide Arm/Group Description:

These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy.

oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability

These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Overall Number of Participants Analyzed 55 41
Measure Type: Count of Participants
Unit of Measure: Participants
5
   9.1%
5
  12.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oseltamirvir, Standard of Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .732
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Primary Outcome
Title Number of Participants That Had Short-term Mortality
Hide Description Number of subjects who died within 30 days of enrollment
Time Frame 30 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oseltamirvir Standard of Care
Hide Arm/Group Description:

These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy.

oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability

These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Overall Number of Participants Analyzed 55 41
Measure Type: Count of Participants
Unit of Measure: Participants
2
   3.6%
1
   2.4%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oseltamirvir, Standard of Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .9999
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Secondary Outcome
Title Days to Reach Clinical Stability
Hide Description Time to clinical improvement. The criteria for clinical improvement were followed during the first week from the day of admission and defined as follows: a) improvement of signs and symptoms of LRTI reported by patient b) afebrile for at least 8 hours, c) decrease in white blood cell count to more than 10% from the prior day, and d) able to tolerate oral feeding. A patient was considered clinically improved on the day that these four criteria were all met.
Time Frame 30 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oseltamirvir Standard of Care
Hide Arm/Group Description:

These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy.

oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability

These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Overall Number of Participants Analyzed 55 41
Median (Inter-Quartile Range)
Unit of Measure: days
2
(0 to 4)
2
(0 to 4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oseltamirvir, Standard of Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .685
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Secondary Outcome
Title Length of Hospital Stay
Hide Description Duration of hospitalization calculated as the day of discharge minus the day of admission.
Time Frame through study completion, up to 30 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oseltamirvir Standard of Care
Hide Arm/Group Description:

These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy.

oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability

These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Overall Number of Participants Analyzed 55 41
Median (Inter-Quartile Range)
Unit of Measure: days
4
(0 to 8)
4.5
(1.5 to 7.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oseltamirvir, Standard of Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .796
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
7.Secondary Outcome
Title Number of Participants With Hospital Mortality.
Hide Description Number of subjects who died while hospitalized
Time Frame through study completion, up to 30 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oseltamirvir Standard of Care
Hide Arm/Group Description:

These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy.

oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability

These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Overall Number of Participants Analyzed 55 41
Measure Type: Count of Participants
Unit of Measure: Participants
1
   1.8%
1
   2.4%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oseltamirvir, Standard of Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .9999
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Oseltamirvir Standard of Care
Hide Arm/Group Description

These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy.

oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability

These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
All-Cause Mortality
Oseltamirvir Standard of Care
Affected / at Risk (%) Affected / at Risk (%)
Total   2/55 (3.64%)      1/41 (2.44%)    
Show Serious Adverse Events Hide Serious Adverse Events
Oseltamirvir Standard of Care
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/55 (0.00%)      1/41 (2.44%)    
Cardiac disorders     
Cardiovascular event  [1]  0/55 (0.00%)  0 1/41 (2.44%)  1
Indicates events were collected by systematic assessment
[1]
Subject was readmitted to the hospital with chest pain and congestive heart failure not related to the drug.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Oseltamirvir Standard of Care
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/55 (0.00%)      0/41 (0.00%)    
The primary limitation of our study that we were not able to reach the number of patients that were estimated in the sample size calculation.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Paula Peyrani
Organization: University Louisville
Phone: 502-852-3905
Responsible Party: Julio Ramirez, University of Louisville
ClinicalTrials.gov Identifier: NCT01248715     History of Changes
Other Study ID Numbers: RETOS
First Submitted: November 23, 2010
First Posted: November 25, 2010
Results First Submitted: August 7, 2017
Results First Posted: September 6, 2017
Last Update Posted: November 6, 2017