Clinical trial NCT03423641: An Observational Study of the Safety of Direct-acting Antivirals in Patients With Hepatitis C
Official title: Safety of Direct-Acting Antiviral Medications for Hepatitis C
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis C, Chronic
Keywords: Drug-Related Side Effects and Adverse Reactions
Antiviral Agents / Adverse Effects
Antiviral Agents / Toxicity
Simeprevir
Sofosbuvir
Ledipasvir
Ombitasvir
Paritaprevir
Ritonavir
Dasabuvir
Daclatasvir
Elbasvir
Grazoprevir
Velpatasvir
Ribavirin
Lead sponsor: Kaiser Permanente
Sponsor class: OTHER
Collaborators: name: OneFlorida Clinical Research Consortium
name: Patient-Centered Outcomes Research Institute
First posted: 2018-02-06
Enrollment: 33808
Sex: ALL
Minimum age (years): 18
Maximum age (years): 88
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The groups/cohorts will consist of all HCV patients from Kaiser Permanente Southern California region, Kaiser Permanente Northern California region, and the OneFlorida Clinical Research Consortium.

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.


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.

The results will be examined for sensitivity to the following possible exclusion criteria:

* 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)

Primary outcomes:
measure: Incidence of Acute Myocardial Infarction (AMI)
timeFrame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
measure: Incidence of Acute on Chronic Liver Failure
timeFrame: Labs and diagnoses collected from clinical encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
measure: Incidence of Acute Kidney Failure (AKF)
timeFrame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
measure: Incidence of Multiple Organ Dysfunction Syndrome (MODS)
timeFrame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
measure: Death
timeFrame: Death dates will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
measure: Incidence of Ischemic Stroke
timeFrame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
measure: Incidence of Hemorrhagic Stroke
timeFrame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
measure: Incidence of Decompensated Cirrhosis
timeFrame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
measure: Rate of Hospitalizations
timeFrame: Hospitalizations will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
measure: Rate of Emergency Department Visits
timeFrame: ED visits will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
measure: Incidence of Arrhythmia
timeFrame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
measure: Incidence of Liver Cancer
timeFrame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
measure: Incidence of Cancers Other Than Liver Cancer
timeFrame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
measure: Incidence of HBV Reactivation
timeFrame: Labs will be for up to 180 days following the initiation of a DAA.
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Kaiser Permanente
name: Elizabeth A McGlynn, PhD
role: PRINCIPAL_INVESTIGATOR
References: