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NCT Number: NCT03423641

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

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.

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Key information

Conditions

Hepatitis C, Chronic Blood-Borne Infections Chemically-Induced Disorders Chronic Disease Communicable Diseases Digestive System Diseases Disease Attributes Drug-Related Side Effects and Adverse Reactions Flaviviridae Infections Hepatitis Hepatitis C Hepatitis, Chronic Hepatitis, Viral, Human Infections Liver Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms RNA Virus Infections Virus Diseases

Age range

18 year–88 year

Sex eligibility

All sexes

Study type

Observational

Who can participate

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Direct Acting Antivirals

Drug

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

Primary outcomes

  1. Incidence of Acute Myocardial Infarction (AMI)

    Time frame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.

    Inpatient encounter with an ICD-9 diagnosis code of 410.xx or ICD-10 diagnosis code of I21.xx.

  2. Incidence of Acute on Chronic Liver Failure

    Time frame: 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.

    An acute change in MELD (model for end stage liver disease) score of 5 or more and the change is deemed to have persisted (defined as meeting one of the following criteria: MELD continues to be elevated 3 months later, liver transplant, death). The minimum value for the MELD is 6.43, but there is no maximum value. Higher scores mean a worse outcome.

  3. Incidence of Acute Kidney Failure (AKF)

    Time frame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.

    Encounters with an ICD-9 diagnosis code of 584.xx or ICD-10 diagnosis code of N17.xx.

  4. Incidence of Multiple Organ Dysfunction Syndrome (MODS)

    Time frame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.

    Inpatient encounters with ICD-9 diagnosis code of 995.92, 995.94, 785.52 or ICD-10 code of R65.11 or R65.2x.

  5. Death

    Time frame: Death dates will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.

    Date of death in one or more records. Death data comes from medical records, Social Security, or state databases.

  6. Incidence of Ischemic Stroke

    Time frame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.

    Inpatient encounters with ICD-9 diagnosis code of 433.xx, 434.xx or ICD-10 code of I63.xx, I65.xx.

  7. Incidence of Hemorrhagic Stroke

    Time frame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.

    Inpatient encounters with ICD-9 diagnosis code of 430.xx-432.xx or ICD-10 code of I60.xx-I62.xx

  8. Incidence of Decompensated Cirrhosis

    Time frame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.

    A patient will be characterized as having decompensated cirrhosis from an encounter indicating jaundice (ICD-9 diagnosis code of 782.4 or ICD-10 code of R17), ascites (ICD-9 diagnosis code of 789.5, 789.51, 789.59 or ICD-10 diagnosis code of R18.0, R18.8, K71.51, K70.11, or K70.31), or varices (ICD-9 diagnosis code of 456.0, 456.20 or ICD-10 diagnosis code of I85.01 or I85.11, or a medication dispense of lactulose or rifaximin along with a diagnosis of cirrhosis.

  9. Rate of Hospitalizations

    Time frame: Hospitalizations will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.

    An encounter in which the place of service is an inpatient hospitalization.

  10. Rate of Emergency Department Visits

    Time frame: ED visits will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.

    An encounter in which the place of service is an emergency department or urgent care center.

  11. Incidence of Arrhythmia

    Time frame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.

    Inpatient encounters with an ICD-9 diagnosis code of 427.1, 427.42, 427.5, 427.9 or an ICD-10 diagnosis code of I47.2, I49.01, I49.02, I46.9, I49.9.

  12. Incidence of Liver Cancer

    Time frame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.

    Encounters with ICD-9 diagnosis code of 155.xx or ICD-10 code of C22.xx.

  13. Incidence of Cancers Other Than Liver Cancer

    Time frame: Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.

    Encounters with ICD-9 codes 140.xx through 208.xx, except 155.xx or ICD-10 coes C00-C97 except C22.xx.

  14. Incidence of HBV Reactivation

    Time frame: Labs will be for up to 180 days following the initiation of a DAA.

    We identified HBV reactivations in three different ways [Di Bisceglie et al., 2015; Yanny et al., 2018]: (1) patients who had a history of Hepatitis B core antibody (HBcAb) positive and were Hepatitis B surface antigen (HBsAg) negative at the time of initiating DAA therapy who became HBsAg positive within 180 days after receiving a DAA; (2) patients with undetectable levels of HBV DNA at the time of initiating DAA therapy who had a numerical result within 180 days after receiving a DAA; (3) patients with a numerical HBV DNA result at the time of initiating DAA therapy whose viral load increased by a factor of 10 within 180 days after receiving a DAA. For all methods of detecting a reactivation, we required that the reactivations be clinically significant: bilirubin at least 3, aspartate aminotransferase (AST) at least 400, or alanine aminotransferase (ALT) at least 500.

Sponsors and collaborators

Lead sponsor

Kaiser Permanente

Other

Collaborators

  • OneFlorida Clinical Research Consortium
  • Patient-Centered Outcomes Research Institute

Registry information

Official study title

Safety of Direct-Acting Antiviral Medications for Hepatitis C

Important dates

Study start
2011
Primary completion
2017
Study completion
2017
First posted
Feb 6, 2018
Registry last updated
Aug 7, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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