N/A
N=33,808
An Observational Study of the Safety of Direct-acting Antivirals in Patients With Hepatitis C
Hepatitis C, Chronic
Bottom Line
View on ClinicalTrials.gov: NCT03423641 ↗Enrolled (actual)
33,808
Serious AEs
0.0%
Results posted
Aug 2019
Primary outcome: Primary: Incidence of Acute Myocardial Infarction (AMI) — 3.3; 5.2 Events per 1000 person years — p=.68
Study Design & Population
- Study type
- Observational
- Phase
- N/A
- Interventions
- Direct Acting Antivirals (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Kaiser Permanente
- Primary completion
- Dec 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence of Acute Myocardial Infarction (AMI) |
3.3; 5.2 | .68 |
| PRIMARY Incidence of Acute on Chronic Liver Failure |
16.5; 24.1 | 0.01 sig |
| PRIMARY Incidence of Acute Kidney Failure (AKF) |
24.2; 33.7 | 0.39 |
| PRIMARY Incidence of Multiple Organ Dysfunction Syndrome (MODS) |
9.7; 17.2 | 0.01 sig |
| PRIMARY Death |
10.7; 33.7 | <0.01 sig |
| PRIMARY Incidence of Ischemic Stroke |
3.6; 5.8 | 0.12 |
| PRIMARY Incidence of Hemorrhagic Stroke |
1.5; 3.1 | 0.34 |
| PRIMARY Incidence of Decompensated Cirrhosis |
23.8; 38.6 | <0.01 sig |
| PRIMARY Rate of Hospitalizations |
162.8; 325.0 | <0.01 sig |
| PRIMARY Rate of Emergency Department Visits |
551.2; 853.4 | <0.01 sig |
| PRIMARY Incidence of Arrhythmia |
3.2; 4.7 | 0.02 sig |
| PRIMARY Incidence of Liver Cancer |
9.3; 14.9 | 0.07 |
| PRIMARY Incidence of Cancers Other Than Liver Cancer |
20.7; 26.4 | 0.11 |
| PRIMARY Incidence of HBV Reactivation |
1 | — |
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)
Data sourced from ClinicalTrials.gov (NCT03423641). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.