ED Influenza Therapeutic Pilot Study: Oseltamivir vs. Peramivir

NCT02609399 | Completed Phase 4 Results FDA Drug

• 3 other identifiers: IRB000804051 IDSEP150026-01-001 IDSEP160031-01-00
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 2

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.

Conditions

Influenza

Keywords

Influenza; Antiviral treatment; Emergency department; Influenza therapeutics; Rapid influenza testing

Outcome Measures

Primary Outcomes (4)

• 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: 1. Not at all 2. A little bit 3. Somewhat 4. Quite a bit 5. Very much

  ED Enrollment Visit through Day 14 ( 2015-2016 influenza season)

• 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: 1. Not at all 2. A little bit 3. Somewhat 4. Quite a bit 5. Very much

  ED Enrollment Visit through Day 14 ( 2016-2017 influenza season)

• 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.

  ED Enrollment Visit through Day 14 ( 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.

  ED Enrollment Visit through Day 14 ( 2016-2017 influenza season)

Study Arms (2)

Oseltamivir

EXPERIMENTAL

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

Drug: Oseltamivir

Peramivir

EXPERIMENTAL

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

Drug: Peramivir

Interventions

Oseltamivir DRUG

Oral

Also known as: Tamiflu

Oseltamivir

Peramivir DRUG

IV Note: Subjects admitted to the hospital directly from the ED Enrollment Visit may receive more doses at the discretion of the treating physician.

Also known as: Rapivab

Peramivir

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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).

You may not qualify if:

• 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:
• a. 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• Department of Health and Human Services: collaborator

Study Sites (2)

Maricopa Integrated Health System

Phoenix, Arizona, 85008, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Influenza, Human; Emergencies

Interventions

Oseltamivir; peramivir

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Limitations and Caveats

1. Not designed or powered to assess differences in clinical outcomes. 2. Planned to recruit \>= 50 subjects/site, but MMC enrolled 44 due to lower-than-expected flu incidence and Hopkins Uni. increased enrollment to make up for the shortfall.

Results Point of Contact

• Title: Dr. Richard Rothman
• Organization: Johns Hopkins University

rrothma1@jhmi.edu

410-735-6428

Study Officials

• Richard Rothman, MD, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2015
• First Posted: November 20, 2015
• Study Start: November 1, 2015
• Primary Completion: May 26, 2017
• Study Completion: May 31, 2018
• Last Updated: October 4, 2019
• Results First Posted: June 20, 2018

Record last verified: 2019-09

Locations

US (2)