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Trial record 82 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03423641
Recruitment Status : Completed
First Posted : February 6, 2018
Results First Posted : August 7, 2019
Last Update Posted : August 7, 2019
Sponsor:
Collaborators:
OneFlorida Clinical Research Consortium
Patient-Centered Outcomes Research Institute
Information provided by (Responsible Party):
Elizabeth A. McGlynn, Kaiser Permanente

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.

Condition or disease Intervention/treatment
Hepatitis C, Chronic Drug: Direct Acting Antivirals

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Study Type : Observational
Actual Enrollment : 33808 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Safety of Direct-Acting Antiviral Medications for Hepatitis C
Actual Study Start Date : January 1, 2011
Actual Primary Completion Date : December 31, 2017
Actual Study Completion Date : December 31, 2017

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Direct Acting Antivirals
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the drug.
Drug: 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.

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)



Primary Outcome Measures :
  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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 88 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03423641


Sponsors and Collaborators
Kaiser Permanente
OneFlorida Clinical Research Consortium
Patient-Centered Outcomes Research Institute
Investigators
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Principal Investigator: Elizabeth A McGlynn, PhD Kaiser Permanente
  Study Documents (Full-Text)

Documents provided by Elizabeth A. McGlynn, Kaiser Permanente:
Statistical Analysis Plan  [PDF] January 31, 2018
Study Protocol  [PDF] June 18, 2019


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Responsible Party: Elizabeth A. McGlynn, Vice President, Kaiser Permanente Research; Executive Director, Center for Effectiveness and Safety Research, Kaiser Permanente
ClinicalTrials.gov Identifier: NCT03423641     History of Changes
Other Study ID Numbers: RI-RCR-1000
First Posted: February 6, 2018    Key Record Dates
Results First Posted: August 7, 2019
Last Update Posted: August 7, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Current plan is to make a de-identified data set available to investigators under specified conditions.

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by Elizabeth A. McGlynn, Kaiser Permanente:
Elbasvir
Grazoprevir
Drug-Related Side Effects and Adverse Reactions
Antiviral Agents / Adverse Effects
Antiviral Agents / Toxicity
Simeprevir
Sofosbuvir
Ledipasvir
Ombitasvir
Paritaprevir
Ritonavir
Dasabuvir
Daclatasvir
Velpatasvir
Ribavirin
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Antiviral Agents
Anti-Infective Agents