Trial Outcomes & Findings for An Observational Study of the Safety of Direct-acting Antivirals in Patients With Hepatitis C (NCT NCT03423641)
NCT ID: NCT03423641
Last Updated: 2019-08-07
Results Overview
Inpatient encounter with an ICD-9 diagnosis code of 410.xx or ICD-10 diagnosis code of I21.xx.
COMPLETED
33808 participants
Patient diagnoses collected from encounters will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
2019-08-07
Participant Flow
This is a retrospective observational study, thus patients are not assigned and no one is excluded from the study after they become eligible.
Participant milestones
| Measure |
Direct Acting Antivirals
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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)
|
|---|---|---|
|
Overall Study
STARTED
|
15524
|
18284
|
|
Overall Study
COMPLETED
|
15193
|
10210
|
|
Overall Study
NOT COMPLETED
|
331
|
8074
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
There is no difference between the baseline population and the analysis population.
Baseline characteristics by cohort
| Measure |
Direct Acting Antivirals
n=15524 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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
n=18284 Participants
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)
|
Total
n=33808 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants • There is no difference between the baseline population and the analysis population.
|
0 Participants
n=107 Participants • There is no difference between the baseline population and the analysis population.
|
0 Participants
n=206 Participants • There is no difference between the baseline population and the analysis population.
|
|
Age, Categorical
Between 18 and 65 years
|
12349 Participants
n=99 Participants • There is no difference between the baseline population and the analysis population.
|
14638 Participants
n=107 Participants • There is no difference between the baseline population and the analysis population.
|
26987 Participants
n=206 Participants • There is no difference between the baseline population and the analysis population.
|
|
Age, Categorical
>=65 years
|
3175 Participants
n=99 Participants • There is no difference between the baseline population and the analysis population.
|
3646 Participants
n=107 Participants • There is no difference between the baseline population and the analysis population.
|
6821 Participants
n=206 Participants • There is no difference between the baseline population and the analysis population.
|
|
Sex: Female, Male
Female
|
6092 Participants
n=99 Participants
|
6962 Participants
n=107 Participants
|
13054 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
9432 Participants
n=99 Participants
|
11322 Participants
n=107 Participants
|
20754 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
112 Participants
n=99 Participants
|
116 Participants
n=107 Participants
|
228 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
891 Participants
n=99 Participants
|
772 Participants
n=107 Participants
|
1663 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
49 Participants
n=99 Participants
|
51 Participants
n=107 Participants
|
100 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2699 Participants
n=99 Participants
|
3838 Participants
n=107 Participants
|
6537 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
8670 Participants
n=99 Participants
|
9892 Participants
n=107 Participants
|
18562 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
700 Participants
n=99 Participants
|
720 Participants
n=107 Participants
|
1420 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2403 Participants
n=99 Participants
|
2895 Participants
n=107 Participants
|
5298 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
15524 Participants
n=99 Participants
|
18284 Participants
n=107 Participants
|
33808 Participants
n=206 Participants
|
PRIMARY outcome
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.Population: The analysis population consists of the subset of patients without a prior diagnosis of MI.
Inpatient encounter with an ICD-9 diagnosis code of 410.xx or ICD-10 diagnosis code of I21.xx.
Outcome measures
| Measure |
Direct Acting Antivirals
n=14959 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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
n=17421 Participants
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)
|
|---|---|---|
|
Incidence of Acute Myocardial Infarction (AMI)
|
3.3 Events per 1000 person years
Interval 2.0 to 4.7
|
5.2 Events per 1000 person years
Interval 4.6 to 5.8
|
PRIMARY outcome
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.Population: The analysis population consists of the subset of patients with MELD scores less than 15 at baseline.
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.
Outcome measures
| Measure |
Direct Acting Antivirals
n=13321 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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
n=13716 Participants
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)
|
|---|---|---|
|
Incidence of Acute on Chronic Liver Failure
|
16.5 Events per 1000 person years
Interval 13.3 to 19.7
|
24.1 Events per 1000 person years
Interval 22.8 to 25.5
|
PRIMARY outcome
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.Population: The analysis population consists of the subset of patients without a prior diagnosis of AKF.
Encounters with an ICD-9 diagnosis code of 584.xx or ICD-10 diagnosis code of N17.xx.
Outcome measures
| Measure |
Direct Acting Antivirals
n=14321 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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
n=16926 Participants
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)
|
|---|---|---|
|
Incidence of Acute Kidney Failure (AKF)
|
24.2 Events per 1000 person years
Interval 20.5 to 28.0
|
33.7 Events per 1000 person years
Interval 32.2 to 35.2
|
PRIMARY outcome
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.Population: The analysis population consists of the subset of patients without a prior diagnosis of MODS.
Inpatient encounters with ICD-9 diagnosis code of 995.92, 995.94, 785.52 or ICD-10 code of R65.11 or R65.2x.
Outcome measures
| Measure |
Direct Acting Antivirals
n=15107 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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
n=17763 Participants
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)
|
|---|---|---|
|
Incidence of Multiple Organ Dysfunction Syndrome (MODS)
|
9.7 Events per 1000 person years
Interval 7.4 to 12.0
|
17.2 Events per 1000 person years
Interval 16.2 to 18.3
|
PRIMARY outcome
Timeframe: Death dates will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.Population: The analysis population is equivalent to the baseline population.
Date of death in one or more records. Death data comes from medical records, Social Security, or state databases.
Outcome measures
| Measure |
Direct Acting Antivirals
n=15524 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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
n=18284 Participants
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)
|
|---|---|---|
|
Death
|
10.7 Events per 1000 person years
Interval 8.3 to 13.1
|
33.7 Events per 1000 person years
Interval 32.3 to 35.1
|
PRIMARY outcome
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.Population: The analysis population consists of the subset of patients without a prior diagnosis of a stroke.
Inpatient encounters with ICD-9 diagnosis code of 433.xx, 434.xx or ICD-10 code of I63.xx, I65.xx.
Outcome measures
| Measure |
Direct Acting Antivirals
n=14758 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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
n=17142 Participants
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)
|
|---|---|---|
|
Incidence of Ischemic Stroke
|
3.6 Events per 1000 person years
Interval 2.2 to 5.1
|
5.8 Events per 1000 person years
Interval 5.1 to 6.4
|
PRIMARY outcome
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.Population: The analysis population consists of the subset of patients without a prior diagnosis of a stroke.
Inpatient encounters with ICD-9 diagnosis code of 430.xx-432.xx or ICD-10 code of I60.xx-I62.xx
Outcome measures
| Measure |
Direct Acting Antivirals
n=14802 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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
n=17098 Participants
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)
|
|---|---|---|
|
Incidence of Hemorrhagic Stroke
|
1.5 Events per 1000 person years
Interval 0.6 to 2.3
|
3.1 Events per 1000 person years
Interval 2.6 to 3.5
|
PRIMARY outcome
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.Population: The analysis population consists of the subset of patients without prior diagnosis of jaundice, ascites, hemorrhagic varices or medication dispense of lactulose or rifaximin.
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.
Outcome measures
| Measure |
Direct Acting Antivirals
n=13496 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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
n=16465 Participants
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)
|
|---|---|---|
|
Incidence of Decompensated Cirrhosis
|
23.8 Events per 1000 person years
Interval 20.0 to 27.7
|
38.6 Events per 1000 person years
Interval 37.0 to 40.2
|
PRIMARY outcome
Timeframe: Hospitalizations will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.Population: The analysis population is the same as the baseline population.
An encounter in which the place of service is an inpatient hospitalization.
Outcome measures
| Measure |
Direct Acting Antivirals
n=15524 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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
n=18284 Participants
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)
|
|---|---|---|
|
Rate of Hospitalizations
|
162.8 Events per 1000 person years
Interval 157.9 to 167.7
|
325.0 Events per 1000 person years
Interval 320.6 to 329.4
|
PRIMARY outcome
Timeframe: ED visits will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.Population: The analysis population is the same as the baseline population.
An encounter in which the place of service is an emergency department or urgent care center.
Outcome measures
| Measure |
Direct Acting Antivirals
n=15524 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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
n=18284 Participants
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)
|
|---|---|---|
|
Rate of Emergency Department Visits
|
551.2 Events per 1000 person years
Interval 542.3 to 560.2
|
853.4 Events per 1000 person years
Interval 846.2 to 860.5
|
PRIMARY outcome
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.Population: The analysis population consists of the subset of patients without a past diagnosis of arrhythmia.
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.
Outcome measures
| Measure |
Direct Acting Antivirals
n=13396 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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
n=15272 Participants
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)
|
|---|---|---|
|
Incidence of Arrhythmia
|
3.2 Events per 1000 person years
Interval 1.8 to 4.5
|
4.7 Events per 1000 person years
Interval 4.1 to 5.2
|
PRIMARY outcome
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.Population: The analysis population consists of the subset of patients without a prior diagnosis of liver cancer.
Encounters with ICD-9 diagnosis code of 155.xx or ICD-10 code of C22.xx.
Outcome measures
| Measure |
Direct Acting Antivirals
n=14905 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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
n=17989 Participants
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)
|
|---|---|---|
|
Incidence of Liver Cancer
|
9.3 Events per 1000 person years
Interval 7.0 to 11.5
|
14.9 Events per 1000 person years
Interval 13.9 to 15.8
|
PRIMARY outcome
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.Population: The analysis population consists of the subset of patients without a prior diagnosis of cancer.
Encounters with ICD-9 codes 140.xx through 208.xx, except 155.xx or ICD-10 coes C00-C97 except C22.xx.
Outcome measures
| Measure |
Direct Acting Antivirals
n=13254 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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
n=16689 Participants
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)
|
|---|---|---|
|
Incidence of Cancers Other Than Liver Cancer
|
20.7 Events per 1000 person years
Interval 17.1 to 24.3
|
26.4 Events per 1000 person years
Interval 25.0 to 27.7
|
PRIMARY outcome
Timeframe: Labs will be for up to 180 days following the initiation of a DAA.Population: At the time of initiating DAA therapy, at least one of the following had to be true (1) Hepatitis B core antibody (HBcAb) positive and Hepatitis B surface antigen (HBsAg) negative (2) Hepatitis B core antibody (HBcAb) positive and undetectable levels of HBV DNA; (3) numerical HBV DNA result
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.
Outcome measures
| Measure |
Direct Acting Antivirals
n=2308 Participants
Patients who receive a direct acting antiviral enter the DAA cohort at the time of initiation of the 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)
|
|---|---|---|
|
Incidence of HBV Reactivation
|
1 Participants
|
—
|
Adverse Events
Direct Acting Antivirals
Comparison
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place