Trial Outcomes & Findings for Rapid Empiric Treatment With Oseltamivir Study (RETOS) (NCT NCT01248715)

NCT ID: NCT01248715

Last Updated: 2023-06-15

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 1107 participants
• Primary outcome timeframe: 7 days
• Results posted on: 2023-06-15

Participant Flow

Participant milestones

Measure	Oseltamirvir 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	Standard of Care 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 Study STARTED	556	551
Overall Study COMPLETED	55	41
Overall Study NOT COMPLETED	501	510

Reasons for withdrawal

Measure	Oseltamirvir 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	Standard of Care 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 Study Not influenza positive	501	510

Baseline Characteristics

Rapid Empiric Treatment With Oseltamivir Study (RETOS)

Baseline characteristics by cohort

Measure	Oseltamirvir n=55 Participants 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	Standard of Care n=41 Participants 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 n=96 Participants Total of all reporting groups
Age, Continuous	63 years n=5 Participants	60 years n=7 Participants	61.7 years n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	18 Participants n=7 Participants	50 Participants n=5 Participants
Region of Enrollment United States	55 Participants n=5 Participants	41 Participants n=7 Participants	96 Participants n=5 Participants
Nursing home Resident	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 7 days

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.

Outcome measures

Measure	Oseltamirvir n=55 Participants 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	Standard of Care n=41 Participants 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.
Number of Participants With Clinical Failure (Failure to Reach Clinical Stability)	6 Participants	2 Participants

PRIMARY outcome

Timeframe: 24 h

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.

Outcome measures

Measure	Oseltamirvir n=55 Participants 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	Standard of Care n=41 Participants 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.
Number of Participants to Transfer to ICU After 24 h	2 Participants	2 Participants

PRIMARY outcome

Timeframe: 30 days

Participants that were re-hospitalized within 30 days after enrollment.

Outcome measures

Measure	Oseltamirvir n=55 Participants 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	Standard of Care n=41 Participants 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.
Number of Participants That Required Re-hospitalization	5 Participants	5 Participants

PRIMARY outcome

Timeframe: 30 days

Number of subjects who died within 30 days of enrollment

Outcome measures

Measure	Oseltamirvir n=55 Participants 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	Standard of Care n=41 Participants 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.
Number of Participants That Had Short-term Mortality	2 Participants	1 Participants

SECONDARY outcome

Timeframe: 30 days

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.

Outcome measures

Measure	Oseltamirvir n=55 Participants 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	Standard of Care n=41 Participants 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.
Days to Reach Clinical Stability	2 days Interval 0.0 to 4.0	2 days Interval 0.0 to 4.0

SECONDARY outcome

Timeframe: through study completion, up to 30 days

Duration of hospitalization calculated as the day of discharge minus the day of admission.

Outcome measures

Measure	Oseltamirvir n=55 Participants 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	Standard of Care n=41 Participants 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.
Length of Hospital Stay	4 days Interval 0.0 to 8.0	4.5 days Interval 1.5 to 7.5

SECONDARY outcome

Timeframe: through study completion, up to 30 days

Number of subjects who died while hospitalized

Outcome measures

Measure	Oseltamirvir n=55 Participants 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	Standard of Care n=41 Participants 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.
Number of Participants With Hospital Mortality.	1 Participants	1 Participants

Adverse Events

Oseltamirvir

Serious events: 0 serious events

Other events: 0 other events

Deaths: 2 deaths

Standard of Care

Serious events: 1 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Measure	Oseltamirvir n=55 participants at risk 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	Standard of Care n=41 participants at risk 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.
Cardiac disorders Cardiovascular event	0.00% 0/55	2.4% 1/41 • Number of events 1

Other adverse events

Adverse event data not reported

Additional Information

Dr. Paula Peyrani

University Louisville

Phone: 502-852-3905

Email: paula.peyrani@louisville.edu

Results disclosure agreements

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