Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

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

5. august 2019 opdateret af: Elizabeth A. McGlynn, Kaiser Permanente

Safety of Direct-Acting Antiviral Medications for 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Observationel

Tilmelding (Faktiske)

33808

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 88 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

N/A

Køn, der er berettiget til at studere

Alle

Prøveudtagningsmetode

Sandsynlighedsprøve

Studiebefolkning

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.

Beskrivelse

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)

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

Kohorter og interventioner

Gruppe / kohorte
Intervention / Behandling
Direct Acting Antivirals
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the drug.
Medicin: 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)

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Incidence of Acute Myocardial Infarction (AMI)
Tidsramme: 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.
Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Incidence of Acute on Chronic Liver Failure
Tidsramme: 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.
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.
Incidence of Acute Kidney Failure (AKF)
Tidsramme: 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.
Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Incidence of Multiple Organ Dysfunction Syndrome (MODS)
Tidsramme: 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.
Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Death
Tidsramme: 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.
Death dates will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Incidence of Ischemic Stroke
Tidsramme: 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.
Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Incidence of Hemorrhagic Stroke
Tidsramme: 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
Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Incidence of Decompensated Cirrhosis
Tidsramme: 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.
Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Rate of Hospitalizations
Tidsramme: 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.
Hospitalizations will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Rate of Emergency Department Visits
Tidsramme: 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.
ED visits will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Incidence of Arrhythmia
Tidsramme: 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.
Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Incidence of Liver Cancer
Tidsramme: 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.
Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Incidence of Cancers Other Than Liver Cancer
Tidsramme: 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.
Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Incidence of HBV Reactivation
Tidsramme: 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.
Labs will be for up to 180 days following the initiation of a DAA.

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Kaiser Permanente

Samarbejdspartnere

Patient-Centered Outcomes Research Institute
OneFlorida Clinical Research Consortium

Efterforskere

  • Ledende efterforsker: Elizabeth A McGlynn, PhD, Kaiser Permanente

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

1. januar 2011

Primær færdiggørelse (Faktiske)

31. december 2017

Studieafslutning (Faktiske)

31. december 2017

Datoer for studieregistrering

Først indsendt

31. januar 2018

Først indsendt, der opfyldte QC-kriterier

31. januar 2018

Først opslået (Faktiske)

6. februar 2018

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

7. august 2019

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

5. august 2019

Sidst verificeret

1. august 2019

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • RI-RCR-1000

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

UBESLUTET

IPD-planbeskrivelse

Current plan is to make a de-identified data set available to investigators under specified conditions.

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Hepatitis C, kronisk

Kliniske forsøg med Direct Acting Antivirals

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Germany

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner