Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
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

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Retrospective
Condition Hepatitis C, Chronic
Intervention Drug: Direct Acting Antivirals
Enrollment 33808
Recruitment Details  
Pre-assignment Details This is a retrospective observational study, thus patients are not assigned and no one is excluded from the study after they become eligible.
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description

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.

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)
Period Title: Overall Study
Started 15524 18284
Completed 15193 10210
Not Completed 331 8074
Arm/Group Title Direct Acting Antivirals Comparison Total
Hide Arm/Group Description

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.

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 of all reporting groups
Overall Number of Baseline Participants 15524 18284 33808
Hide Baseline Analysis Population Description
There is no difference between the number of baseline participants and the numbers in participant flow.
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15524 participants 18284 participants 33808 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
12349
  79.5%
14638
  80.1%
26987
  79.8%
>=65 years
3175
  20.5%
3646
  19.9%
6821
  20.2%
[1]
Measure Analysis Population Description: There is no difference between the baseline population and the analysis population.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15524 participants 18284 participants 33808 participants
Female
6092
  39.2%
6962
  38.1%
13054
  38.6%
Male
9432
  60.8%
11322
  61.9%
20754
  61.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15524 participants 18284 participants 33808 participants
American Indian or Alaska Native
112
   0.7%
116
   0.6%
228
   0.7%
Asian
891
   5.7%
772
   4.2%
1663
   4.9%
Native Hawaiian or Other Pacific Islander
49
   0.3%
51
   0.3%
100
   0.3%
Black or African American
2699
  17.4%
3838
  21.0%
6537
  19.3%
White
8670
  55.8%
9892
  54.1%
18562
  54.9%
More than one race
700
   4.5%
720
   3.9%
1420
   4.2%
Unknown or Not Reported
2403
  15.5%
2895
  15.8%
5298
  15.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 15524 participants 18284 participants 33808 participants
15524
 100.0%
18284
 100.0%
33808
 100.0%
1.Primary Outcome
Title Incidence of Acute Myocardial Infarction (AMI)
Hide Description Inpatient encounter with an ICD-9 diagnosis code of 410.xx or ICD-10 diagnosis code of I21.xx.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of the subset of patients without a prior diagnosis of MI.
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 14959 17421
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 1000 person years
3.3
(2.0 to 4.7)
5.2
(4.6 to 5.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Direct Acting Antivirals, Comparison
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .68
Comments [Not Specified]
Method Marginal Structural Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value .81
Confidence Interval (2-Sided) 95%
0.30 to 2.20
Estimation Comments The numerator represents the DAA group while the denominator represents the comparison group for the odds ratio.
2.Primary Outcome
Title Incidence of Acute on Chronic Liver Failure
Hide Description 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of the subset of patients with MELD scores less than 15 at baseline.
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 13321 13716
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 1000 person years
16.5
(13.3 to 19.7)
24.1
(22.8 to 25.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Direct Acting Antivirals, Comparison
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method Marginal Structural Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.56 to 0.91
Estimation Comments The numerator represents the DAA group while the denominator represents the comparison group for the odds ratio.
3.Primary Outcome
Title Incidence of Acute Kidney Failure (AKF)
Hide Description Encounters with an ICD-9 diagnosis code of 584.xx or ICD-10 diagnosis code of N17.xx.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of the subset of patients without a prior diagnosis of AKF.
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 14321 16926
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 1000 person years
24.2
(20.5 to 28.0)
33.7
(32.2 to 35.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Direct Acting Antivirals, Comparison
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.39
Comments [Not Specified]
Method Marginal Structural Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.75 to 1.12
Estimation Comments The numerator represents the DAA group while the denominator represents the comparison group for the odds ratio.
4.Primary Outcome
Title Incidence of Multiple Organ Dysfunction Syndrome (MODS)
Hide Description Inpatient encounters with ICD-9 diagnosis code of 995.92, 995.94, 785.52 or ICD-10 code of R65.11 or R65.2x.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of the subset of patients without a prior diagnosis of MODS.
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 15107 17763
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 1000 person years
9.7
(7.4 to 12.0)
17.2
(16.2 to 18.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Direct Acting Antivirals, Comparison
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method Marginal Structural Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.49 to 0.90
Estimation Comments The numerator represents the DAA group while the denominator represents the comparison group for the odds ratio.
5.Primary Outcome
Title Death
Hide Description Date of death in one or more records. Death data comes from medical records, Social Security, or state databases.
Time Frame Death dates will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population is equivalent to the baseline population.
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 15524 18284
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 1000 person years
10.7
(8.3 to 13.1)
33.7
(32.3 to 35.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Direct Acting Antivirals, Comparison
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Marginal Structural Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.30 to 0.59
Estimation Comments The numerator represents the DAA group while the denominator represents the comparison group for the odds ratio.
6.Primary Outcome
Title Incidence of Ischemic Stroke
Hide Description Inpatient encounters with ICD-9 diagnosis code of 433.xx, 434.xx or ICD-10 code of I63.xx, I65.xx.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of the subset of patients without a prior diagnosis of a stroke.
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 14758 17142
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 1000 person years
3.6
(2.2 to 5.1)
5.8
(5.1 to 6.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Direct Acting Antivirals, Comparison
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments [Not Specified]
Method Marginal Structural Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.42 to 1.10
Estimation Comments The numerator represents the DAA group while the denominator represents the comparison group for the odds ratio.
7.Primary Outcome
Title Incidence of Hemorrhagic Stroke
Hide Description Inpatient encounters with ICD-9 diagnosis code of 430.xx-432.xx or ICD-10 code of I60.xx-I62.xx
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of the subset of patients without a prior diagnosis of a stroke.
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 14802 17098
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 1000 person years
1.5
(0.6 to 2.3)
3.1
(2.6 to 3.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Direct Acting Antivirals, Comparison
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.34
Comments [Not Specified]
Method Marginal Structural Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.22 to 1.70
Estimation Comments The numerator represents the DAA group while the denominator represents the comparison group for the odds ratio.
8.Primary Outcome
Title Incidence of Decompensated Cirrhosis
Hide Description 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of the subset of patients without prior diagnosis of jaundice, ascites, hemorrhagic varices or medication dispense of lactulose or rifaximin.
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 13496 16465
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 1000 person years
23.8
(20.0 to 27.7)
38.6
(37.0 to 40.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Direct Acting Antivirals, Comparison
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Marginal Structural Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Marginal Structural Model
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.49 to 0.76
Estimation Comments The numerator represents the DAA group while the denominator represents the comparison group for the odds ratio.
9.Primary Outcome
Title Rate of Hospitalizations
Hide Description An encounter in which the place of service is an inpatient hospitalization.
Time Frame Hospitalizations will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population is the same as the baseline population.
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 15524 18284
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 1000 person years
162.8
(157.9 to 167.7)
325.0
(320.6 to 329.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Direct Acting Antivirals, Comparison
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Poisson Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.60 to 0.84
Estimation Comments The numerator represents the DAA group while the denominator represents the comparison group for the rate ratio.
10.Primary Outcome
Title Rate of Emergency Department Visits
Hide Description An encounter in which the place of service is an emergency department or urgent care center.
Time Frame ED visits will be examined through study completion, or up to 180 days from the day the patient initiated a DAA.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population is the same as the baseline population.
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 15524 18284
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 1000 person years
551.2
(542.3 to 560.2)
853.4
(846.2 to 860.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Direct Acting Antivirals, Comparison
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Poisson Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.77 to 0.87
Estimation Comments The numerator represents the DAA group while the denominator represents the comparison group for the rate ratio.
11.Primary Outcome
Title Incidence of Arrhythmia
Hide Description 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of the subset of patients without a past diagnosis of arrhythmia.
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 13396 15272
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 1000 person years
3.2
(1.8 to 4.5)
4.7
(4.1 to 5.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Direct Acting Antivirals, Comparison
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Marginal Structural Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.25 to 0.88
Estimation Comments The numerator represents the DAA group while the denominator represents the comparison group for the odds ratio.
12.Primary Outcome
Title Incidence of Liver Cancer
Hide Description Encounters with ICD-9 diagnosis code of 155.xx or ICD-10 code of C22.xx.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of the subset of patients without a prior diagnosis of liver cancer.
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 14905 17989
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 1000 person years
9.3
(7.0 to 11.5)
14.9
(13.9 to 15.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Direct Acting Antivirals, Comparison
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments [Not Specified]
Method Marginal Structural Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.37 to 1.03
Estimation Comments The numerator represents the DAA group while the denominator represents the comparison group for the odds ratio.
13.Primary Outcome
Title Incidence of Cancers Other Than Liver Cancer
Hide Description Encounters with ICD-9 codes 140.xx through 208.xx, except 155.xx or ICD-10 coes C00-C97 except C22.xx.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of the subset of patients without a prior diagnosis of cancer.
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 13254 16689
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 1000 person years
20.7
(17.1 to 24.3)
26.4
(25.0 to 27.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Direct Acting Antivirals, Comparison
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments [Not Specified]
Method Marginal Structural Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.63 to 1.05
Estimation Comments The numerator represents the DAA group while the denominator represents the comparison group for the odds ratio.
14.Primary Outcome
Title Incidence of HBV Reactivation
Hide Description 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.
Time Frame Labs will be for up to 180 days following the initiation of a DAA.
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Direct Acting Antivirals
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 2308
Measure Type: Count of Participants
Unit of Measure: Participants
1
   0.0%
Time Frame This was a retrospective observational study, so any adverse event data would have been collected during contact with a medical provider.
Adverse Event Reporting Description This was a retrospective observational study. Any adverse event reporting would have been the responsibility of the medical provider. We did not seek out adverse event information above and beyond the outcomes of interest in our study.
 
Arm/Group Title Direct Acting Antivirals Comparison
Hide Arm/Group Description

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.

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)
All-Cause Mortality
Direct Acting Antivirals Comparison
Affected / at Risk (%) Affected / at Risk (%)
Total   77/15524 (0.50%)   2186/18284 (11.96%) 
Show Serious Adverse Events Hide Serious Adverse Events
Direct Acting Antivirals Comparison
Affected / at Risk (%) Affected / at Risk (%)
Total   0/15524 (0.00%)   0/18284 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Direct Acting Antivirals Comparison
Affected / at Risk (%) Affected / at Risk (%)
Total   0/15524 (0.00%)   0/18284 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Elizabeth McGlynn, Ph.D.
Organization: Kaiser Permanente
Phone: 6265643807
EMail: Elizabeth.A.Mcglynn@kp.org
Layout table for additonal information
Responsible Party: Elizabeth A. McGlynn, Kaiser Permanente
ClinicalTrials.gov Identifier: NCT03423641     History of Changes
Other Study ID Numbers: RI-RCR-1000
First Submitted: January 31, 2018
First Posted: February 6, 2018
Results First Submitted: December 1, 2018
Results First Posted: August 7, 2019
Last Update Posted: August 7, 2019