An Observational Study of the Safety of Direct-acting Antivirals in Patients With Hepatitis C

NCT ID: NCT03423641

Last Updated: 2019-08-07

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 33808 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-01-01
• Study Completion Date: 2017-12-31

Brief Summary

The investigators will assess whether patients with the Hepatitis C virus (HCV) who are prescribed direct-acting antiviral (DAA) medications experience higher rates of adverse events than patients with HCV who are untreated. The investigators hypothesize that patients receiving DAAs do not experience higher rates of adverse events compared to patients who have not received DAAs. The study population is adults between the ages of 18 and 88 with any indication of a diagnosis of HCV. An intervention group (those receiving a DAA) and comparison group (those who are not treated) will be created using medication dispensing data. Eligibility for the study will be determined from January 1, 2011 through December 31, 2017. Covariates will be collected from January 1, 2011 through December 31, 2017. Individual study sites may have access to historical data prior to 2011 that can be used as covariates or to identify individuals with HCV. The primary outcomes of interest include acute myocardial infarction, neurological outcomes (e.g. acute stroke, intracranial bleed), acute kidney failure, acute on chronic liver failure, hepatic decompensation, multiple organ dysfunction syndrome, cancer, bradyarrhythmia, and death. The secondary outcomes include decompensated cirrhosis, hospitalization, emergency department visit, and arrhythmia. Outcomes will be assessed from January 1, 2011 through December 31, 2017. The investigators will use two different analytic approaches to answer the question of interest: a Poisson regression model and marginal structural modeling (MSM). The simpler Poisson model is an extension of tabular rate of event analysis. The more complicated MSM model incorporates modeling of the treatment decision to more flexibly control for confounding by indication. For each outcome, the investigators will only record the first date an outcome occurs. Each outcome will be modeled separately.

Conditions

Hepatitis C, Chronic

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Direct Acting Antivirals

Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the drug.

Direct Acting Antivirals

Intervention Type: DRUG

The time period during which a patient is dispensed the medication and for up to 180 days after initiation of the medication.

Comparison

The exposure time of patients who have not received a direct acting antiviral (patients can change from the comparison to the DAA group once they receive the medication)

No interventions assigned to this group

Interventions

Direct Acting Antivirals

The time period during which a patient is dispensed the medication and for up to 180 days after initiation of the medication.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• HCV viral load
• HCV genotype
• HCV qualitative
• HCV antibody
• HCV drug
• Continuously enrolled 12 months

Exclusion Criteria

• Each outcome will be analyzed separately as time to first event, thus people who experience an outcome prior to their study start date are ineligible for analyses related to that particular outcome.

• Achieved SVR-12 prior to index date
• HCV treatment experienced prior to index date
• No visit in GI, Infectious Disease, or Liver Transplant / Hepatology
• No positive HCV test (genotype, viral load, or qualitative)
• No recent positive HCV test (genotype, viral load or qualitative)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 88 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

OneFlorida Clinical Research Consortium

OTHER

Sponsor Role: collaborator

Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role: collaborator

Kaiser Permanente

OTHER

Sponsor Role: lead

Responsible Party

Elizabeth A. McGlynn

Vice President, Kaiser Permanente Research; Executive Director, Center for Effectiveness and Safety Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elizabeth A McGlynn, PhD

Role: PRINCIPAL_INVESTIGATOR

Kaiser Permanente

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

RI-RCR-1000

Identifier Type: -

Identifier Source: org_study_id