Impact of Obesity on Clinical Outcomes in Patients Receiving Acyclovir for HSV Encephalitis"

Impact of Dosing Weight on Clinical Outcomes in Obese Patients Receiving Acyclovir for HSV Encephalitis (ID-OPRAH)

Multicenter retrospective chart review of patients admitted to any of the six study centers (SSM Health - St. Clare, St. Mary's, Saint Louis University Hospital, St. Anthony's, St. Mary's Madison, Rush University Medical Center, or Methodist Dallas Medical Center) between January 1, 2013 and December 31, 2019 will be conducted. All study centers utilize Epic ® electronic health record (Verona, Wisconsin; www.epic.com) for which all data will be extracted from. Each study center will obtain individual IRB approval prior to data collection. SSM - St. Clare will serve as the lead center for the study with all other centers sending collected and de-identified data to this central site for analysis.

Study Overview

• Status: Completed
• Conditions: HSV Encephalitis
• Intervention / Treatment: Other: To assess the clinical impact of dosing acyclovir based on IBW or adjBW for HSV encephalitis to definitively guide safe and effective therapy.

Detailed Description

• Obese - WHO definition: Body Mass Index > 30 kg/m2
• Ideal Body Weight (IBW) (male) - 50.0 kg + 2.3 kg x (patient height in inches, above 60 inches)
• Ideal Body Weight (female) - 45.5 kg + 2.3 kg x (patient height inches, above 60 inches)
• Adjusted Body Weight - IBW + [0.4 x (ABW - IBW)]
• HSV encephalitis - PCR positive for HSV-1 or HSV-2 in CSF during index admission
• Baseline Serum Creatinine (S Cr) - The SCr value obtained before the start of acyclovir therapy on which the dose of acyclovir should be based upon
• Acute Kidney Injury (AKI) - per RIFLE criteria and while receiving acyclovir: SCr doubles or urine output < 0.5 mL/kg/hour for 12 hours
• End-stage renal disease (ESRD) on admission - mention of a diagnosis of ESRD in electronic medical records prior to receipt of acyclovir
• Guideline-approved, weight-based doses - within 10% of 10 mg/kg dose (to account for rounding due to vial size)
• Adequate hydration - IV fluid order (other than KVO [keep vein open]) within 24 hours before acyclovir start AND either IV fluid order (other than KVO) for majority of acyclovir course or IV fluid + oral diet for majority of acyclovir course
• Appropriately renally dose-adjusted doses - Frequency of acyclovir matches package insert recommendations based on creatinine clearance at baseline
• Interacting medications - Mycophenolate, probenecid, zidovudine, tenofovir, valproic acid, phenytoin

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75237
      • Methodist Charlton Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

• More than one dosing weight strategy utilized for > 24 hours for IV acyclovir dosing during the index admission
• Patients transferred to the hospital already on IV acyclovir for HSV encephalitis
• ESRD on admission
• Concomitant pathogen causing meningitis or encephalitis
• Oral acyclovir used for treatment

Description

Inclusion Criteria:

• Patients Admitted to a SSM Health - St. Clare (STL), St. Mary's (STL), Saint Louis University Hospital (STL), St. Anthony's (OKC), St. Mary's Madison (WIS), Rush University Medical Center (RUMC), or Methodist Dallas Medical Center
• > 18 years old
• Positive cerebrospinal fluid (CSF) PCR for HSV-1 or HSV-2
• BMI > 30 kg/m2
• Received guideline-approved, weight-based doses of IV acyclovir for HSV encephalitis for at least 72 hours during the index admission
• Received appropriately renal dose-adjusted doses of IV acyclovir per package insert recommendations

Exclusion Criteria:

• More than one dosing weight strategy utilized for > 24 hours for IV acyclovir dosing during the index admission
• Patients transferred to the hospital already on IV acyclovir for HSV encephalitis
• ESRD on admission
• Concomitant pathogen causing meningitis or encephalitis
• Oral acyclovir used for treatment

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-hospital mortality	Will assess the clinical impact of dosing acyclovir based on IBW or adjBW for HSV encephalitis	Over 1 month

Collaborators and Investigators

• Sponsor: Methodist Health System
• Investigators: Principal Investigator: Matthew Crotty, PharmD, Methodist Dallas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2021
• Primary Completion (Actual): February 21, 2023
• Study Completion (Actual): April 12, 2023

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: November 9, 2021
• First Posted (Actual): November 19, 2021

Study Record Updates

• Last Update Posted (Actual): July 7, 2023
• Last Update Submitted That Met QC Criteria: July 6, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Virus Diseases; Infections; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; DNA Virus Infections; Herpesviridae Infections; Neuroinflammatory Diseases; Encephalitis; Encephalitis, Herpes Simplex; Anti-Infective Agents; Antiviral Agents; Acyclovir
• Other Study ID Numbers: 007.PHA.2020.A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No