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ED Influenza Therapeutic Pilot Study: Oseltamivir vs. Peramivir

Primary Purpose

Influenza

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Oseltamivir
Peramivir
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Influenza focused on measuring Influenza, Antiviral treatment, Emergency department, Influenza therapeutics, Rapid influenza testing

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Eligible patients include all patients who present to the emergency department (ED) between November and April of each influenza season, or later, at the Co-PIs' discretion, based on influenza prevalence, with the following criteria:

    1. 18 years of age or older
    2. Laboratory confirmed positive influenza test associated with their current ED visit
    3. Symptoms of acute respiratory illness for ≤4 days (96 hours)
    4. Meets CDC criteria for antiviral treatment
  • For the purpose of this study, acute respiratory illness is defined as presence of any of the following symptoms: new or increased cough, new or increased shortness of breath, change in sputum production (for adults 65 years or older), sinus pain, nasal congestion, rhinorrhea, sore throat, subjective fever reported at time of triage or documented fever (defined here as ≥ 38 degrees Celsius).
  • CDC criteria for influenza antiviral treatment is defined as: being age 65 years old or older, pregnant or less than two weeks postpartum, American Indian or Alaska native, morbid obesity (BMI ≥40), a current resident of nursing home or other chronic-care facility, having chronic pulmonary disease, cardiovascular disease (except hypertension alone), renal disease, hepatic disease, hematologic disease, metabolic disorders, neurologic and neurodevelopment conditions, immunosuppression (including that caused by medications or by HIV infection), being admitted to inpatient or an observation unit, or having a clinical diagnosis of pneumonia (by the ED physician).

Exclusion Criteria:

  1. Does not speak and understand English (or English or Spanish)
  2. Unable or unwilling to provide informed consent
  3. Previously enrolled in the study during the current influenza season
  4. Unable to take oral medication
  5. Unable to comply with all planned study procedures including availability for follow-up and willingness to complete study diary and self-assessment
  6. Use of neuraminidase inhibitors within the past seven days
  7. Known allergic reaction to neuraminidase inhibitors
  8. Pregnant or breastfeeding
  9. End-stage renal disease, defined as 9a. Currently undergoing dialysis (either hemo or peritoneal); or 9b. Creatinine clearance (CrCl) of <10 mL/min.
  10. End-stage liver disease, as determined by the treating ED provider
  11. Glucose-6-phosphate dehydrogenase (G6PD) deficiency by patient report
  12. Immunodeficiency, defined as:

12a. Solid organ transplant patients receiving immunosuppression; 12b. Hematopoietic stem cell transplant patients within 12 months of transplant or with ongoing immunosuppression; 12c. Oncology patients who have had chemotherapy within the past 30 days; 12d. Current treatment with steroids equivalent to 10 mg of prednisone or more per day for greater than two weeks; 12e. Rheumatologic patients receiving immunosuppressive therapy; or 12f. HIV patients who meet one of the following criteria: 12fi. Have a cluster of differentiation 4 (CD4) cell count of <200 cells/mm3 within the past 3 months ; 12fii. Not actively receiving highly active antiretroviral therapy (HAART); or 12fiii. Have an absolute lymphocyte count <1.0 x 103 cells/μL conducted at the current ED visit

Sites / Locations

  • Maricopa Integrated Health System
  • Johns Hopkins Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Oseltamivir

Peramivir

Arm Description

Subjects randomized to the oral treatment arm will receive 5 days of oral oseltamivir.

Subjects randomized to the IV treatment group will receive 1 dose of IV peramivir.

Outcomes

Primary Outcome Measures

Mean Symptom Severity Score During the 2015-2016 Influenza Season for Symptom Domains as Assessed Using the Influenza-Patient Reported Outcome (FLU-PRO™) Questionnaire
Symptom evaluation during the 2015-2016 influenza season as recorded through FLU-PRO™: a daily diary developed to assess occurrence and severity of influenza symptoms. Item responses: Not at all A little bit Somewhat Quite a bit Very much
Mean Symptom Severity Score During the 2016-2017 Influenza Season for Symptom Domains as Assessed Using the FLU-PRO™ Questionnaire
Symptom evaluation during the 2016-2017 influenza season as recorded through FLU-PRO™: a daily diary developed to assess occurrence and severity of influenza symptoms. Item responses: Not at all A little bit Somewhat Quite a bit Very much
Mean Karnofsky Performance Scale Score During the 2015-2016 Influenza Season
The Karnofsky Performance Scale is a tool for assessing subject functional impairment. Subjects provided or received (from a healthcare provider such as a doctor or nurse) a daily rating from 0 (Dead) to 100 (Normal - no complaints, no evidence of disease) from enrollment through Day 14 of the 2015-2016 influenza season.
Mean Karnofsky Performance Scale Score During the 2016-2017 Influenza Season
The Karnofsky Performance Scale is a tool for assessing subject functional impairment. Subjects provided or received (from a healthcare provider such as a doctor or nurse) a daily rating from 0 (Dead) to 100 (Normal - no complaints, no evidence of disease) from enrollment through Day 14 of the 2016-2017 influenza season.

Secondary Outcome Measures

Full Information

First Posted
October 27, 2015
Last Updated
September 20, 2019
Sponsor
Johns Hopkins University
Collaborators
Department of Health and Human Services
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1. Study Identification

Unique Protocol Identification Number
NCT02609399
Brief Title
ED Influenza Therapeutic Pilot Study: Oseltamivir vs. Peramivir
Official Title
Influenza Therapeutic Trial: A Pilot Randomized Controlled Trial for Feasibility of Enrolling Subjects for Influenza Therapeutic Trials and Administering Influenza Antivirals in the Emergency Department to High Risk Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
November 1, 2015 (Actual)
Primary Completion Date
May 26, 2017 (Actual)
Study Completion Date
May 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
Department of Health and Human Services

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This pilot study is designed to demonstrate the feasibility of utilizing Emergency Departments (EDs) as a primary site for subject enrollment in clinical trials evaluating influenza therapeutics, and to provide pilot data for future clinical trial design and planning. Primary Objective: To prospectively enroll high-risk subjects with laboratory-confirmed influenza into a randomized, open label study of oral versus IV influenza therapeutic to include symptom evaluation and outcome assessments. Secondary Objective 1: To identify influenza positive patients utilizing a previously established triage-based assessment and rapid testing algorithm for suspected influenza infection. Secondary Objective 2: To retrospectively evaluate all potentially eligible patients for potential enrollment biases. Secondary Objective 3: To create a repository of residual nasopharyngeal samples collected from ED patients with suspected influenza illness.
Detailed Description
Title: A Pilot Randomized Controlled Trial for Feasibility of Enrolling Subjects for Influenza Therapeutic Trials and Administering Influenza Antivirals in the Emergency Department to High Risk Subjects Population: Adults presenting to the emergency department (ED) with laboratory confirmed influenza who meet Centers for Disease Control and Prevention (CDC) criteria for antiviral treatment Informed consent: Written informed consent Number of Sites: 2 - large, urban, academically-affiliated, US EDs Study Duration: November 2015 - June 2018 Subject Participation Duration: 4 weeks Description of Agent or Intervention: Subjects will be randomized to either oral (oseltamivir) or intravenous (IV) (peramivir) antiviral treatment. Description of Study Design: This is an open-label randomized controlled clinical trial in which subjects with influenza are randomized to either oral (oseltamivir) or IV (peramivir) antiviral treatment. Estimated Time to Complete Enrollment: Subject enrollment will occur over two influenza seasons (November 2015 - April 2016 and November 2016 - April 2017) or longer, at the Principal Investigator's discretion, based on influenza prevalence.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza
Keywords
Influenza, Antiviral treatment, Emergency department, Influenza therapeutics, Rapid influenza testing

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
180 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Oseltamivir
Arm Type
Experimental
Arm Description
Subjects randomized to the oral treatment arm will receive 5 days of oral oseltamivir.
Arm Title
Peramivir
Arm Type
Experimental
Arm Description
Subjects randomized to the IV treatment group will receive 1 dose of IV peramivir.
Intervention Type
Drug
Intervention Name(s)
Oseltamivir
Other Intervention Name(s)
Tamiflu
Intervention Description
Oral
Intervention Type
Drug
Intervention Name(s)
Peramivir
Other Intervention Name(s)
Rapivab
Intervention Description
IV Note: Subjects admitted to the hospital directly from the ED Enrollment Visit may receive more doses at the discretion of the treating physician.
Primary Outcome Measure Information:
Title
Mean Symptom Severity Score During the 2015-2016 Influenza Season for Symptom Domains as Assessed Using the Influenza-Patient Reported Outcome (FLU-PRO™) Questionnaire
Description
Symptom evaluation during the 2015-2016 influenza season as recorded through FLU-PRO™: a daily diary developed to assess occurrence and severity of influenza symptoms. Item responses: Not at all A little bit Somewhat Quite a bit Very much
Time Frame
ED Enrollment Visit through Day 14 ( 2015-2016 influenza season)
Title
Mean Symptom Severity Score During the 2016-2017 Influenza Season for Symptom Domains as Assessed Using the FLU-PRO™ Questionnaire
Description
Symptom evaluation during the 2016-2017 influenza season as recorded through FLU-PRO™: a daily diary developed to assess occurrence and severity of influenza symptoms. Item responses: Not at all A little bit Somewhat Quite a bit Very much
Time Frame
ED Enrollment Visit through Day 14 ( 2016-2017 influenza season)
Title
Mean Karnofsky Performance Scale Score During the 2015-2016 Influenza Season
Description
The Karnofsky Performance Scale is a tool for assessing subject functional impairment. Subjects provided or received (from a healthcare provider such as a doctor or nurse) a daily rating from 0 (Dead) to 100 (Normal - no complaints, no evidence of disease) from enrollment through Day 14 of the 2015-2016 influenza season.
Time Frame
ED Enrollment Visit through Day 14 ( 2015-2016 influenza season)
Title
Mean Karnofsky Performance Scale Score During the 2016-2017 Influenza Season
Description
The Karnofsky Performance Scale is a tool for assessing subject functional impairment. Subjects provided or received (from a healthcare provider such as a doctor or nurse) a daily rating from 0 (Dead) to 100 (Normal - no complaints, no evidence of disease) from enrollment through Day 14 of the 2016-2017 influenza season.
Time Frame
ED Enrollment Visit through Day 14 ( 2016-2017 influenza season)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Eligible patients include all patients who present to the emergency department (ED) between November and April of each influenza season, or later, at the Co-PIs' discretion, based on influenza prevalence, with the following criteria: 18 years of age or older Laboratory confirmed positive influenza test associated with their current ED visit Symptoms of acute respiratory illness for ≤4 days (96 hours) Meets CDC criteria for antiviral treatment For the purpose of this study, acute respiratory illness is defined as presence of any of the following symptoms: new or increased cough, new or increased shortness of breath, change in sputum production (for adults 65 years or older), sinus pain, nasal congestion, rhinorrhea, sore throat, subjective fever reported at time of triage or documented fever (defined here as ≥ 38 degrees Celsius). CDC criteria for influenza antiviral treatment is defined as: being age 65 years old or older, pregnant or less than two weeks postpartum, American Indian or Alaska native, morbid obesity (BMI ≥40), a current resident of nursing home or other chronic-care facility, having chronic pulmonary disease, cardiovascular disease (except hypertension alone), renal disease, hepatic disease, hematologic disease, metabolic disorders, neurologic and neurodevelopment conditions, immunosuppression (including that caused by medications or by HIV infection), being admitted to inpatient or an observation unit, or having a clinical diagnosis of pneumonia (by the ED physician). Exclusion Criteria: Does not speak and understand English (or English or Spanish) Unable or unwilling to provide informed consent Previously enrolled in the study during the current influenza season Unable to take oral medication Unable to comply with all planned study procedures including availability for follow-up and willingness to complete study diary and self-assessment Use of neuraminidase inhibitors within the past seven days Known allergic reaction to neuraminidase inhibitors Pregnant or breastfeeding End-stage renal disease, defined as 9a. Currently undergoing dialysis (either hemo or peritoneal); or 9b. Creatinine clearance (CrCl) of <10 mL/min. End-stage liver disease, as determined by the treating ED provider Glucose-6-phosphate dehydrogenase (G6PD) deficiency by patient report Immunodeficiency, defined as: 12a. Solid organ transplant patients receiving immunosuppression; 12b. Hematopoietic stem cell transplant patients within 12 months of transplant or with ongoing immunosuppression; 12c. Oncology patients who have had chemotherapy within the past 30 days; 12d. Current treatment with steroids equivalent to 10 mg of prednisone or more per day for greater than two weeks; 12e. Rheumatologic patients receiving immunosuppressive therapy; or 12f. HIV patients who meet one of the following criteria: 12fi. Have a cluster of differentiation 4 (CD4) cell count of <200 cells/mm3 within the past 3 months ; 12fii. Not actively receiving highly active antiretroviral therapy (HAART); or 12fiii. Have an absolute lymphocyte count <1.0 x 103 cells/μL conducted at the current ED visit
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Rothman, MD, PhD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Maricopa Integrated Health System
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85008
Country
United States
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States

12. IPD Sharing Statement

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ED Influenza Therapeutic Pilot Study: Oseltamivir vs. Peramivir

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