Hepatitis C, Respiratory Failure
Conditions
Keywords
Lung disease, Lung Transplant, HCV, Hepatitis C
Brief summary
This is a proof of concept, single center study for the donation of HCV-positive lungs to HCV negative recipient patients, with preemptive, interventional treatment with 8 weeks of commercially available DAA therapy to prevent HCV transmission upon transplantation.
Detailed description
The goal of this study is to determine if preoperative dosing and sustained administration of pan-genotypic DAA therapy after lungs transplantation prevents the transmission of hepatitis C virus (HCV) infection from an HCVpositive donor lung to an HCV naïve recipient.
Interventions
DRUGClinically prescribed direct acting antiviral (Mavyret or Epclusa) HCV treatment for 8 weeks
8 weeks of direct acting antiviral treatment based on clinical indication (either Mavyret or Epclusa)
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Met MGH transplant center criteria, listed for lung transplant * Able to sign informed consent
Exclusion criteria
* Pregnant or nursing (lactating) women * HIV positivity * Any contra-indication to lung transplantation per center protocol * For study patients in whom Epclusa® therapy is being considered,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Undetectable Blood HCV RNA Level | 12 weeks post last dose of treatment with DAA | Negative HCV RNA by blood testing at 12 weeks after the last dose of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events | 8 weeks | Safety and tolerability of DAA therapy in the lung transplant recipient monitored by quantifying the number of treatment related adverese events per patient and evaluation clinically significant out of range lab results as compared to baseline/pretreatment values per patient |
| Tolerability (Based on Number of Adverse Events and Clinically Significant Laboratory Values) | 8 weeks | Tolerability of commercially available DAA therapy in the lung transplant patient will be monitored by quantifying the number of treatment related adverse events per patient and evaluating clinically significant laboratory results |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred between February 2019 and December 2020.
Pre-assignment details
19 subjects received transplant with an HCV Ab positive organ. 3 of the 19 subjects received an HCV Ab positive/HCV RNA negation (NAT negative) transplant and did not irequire DAA therapy per protocol. 16 subjects received HCV Ab positive/HCV RNA positive (NAT positive) transplant and initiated DAA therapy.
Participants by arm
| Arm | Count |
|---|---|
| Treatment With Direct Acting Antiviral for HCV 8 weeks of treatment with HCV Direct Acting Antiviral tablet (Mavyret)
Clinically prescribed direct acting antiviral (Mavyret) HCV treatment for 8 weeks: 8 weeks of direct acting antiviral treatment based on clinical indication (either Mavyret) | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Treatment With Direct Acting Antiviral for HCV |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Recipient HCV negative status at time of consent | 16 Participants |
| Region of Enrollment United States | 16 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 16 |
| other Total, other adverse events | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Undetectable Blood HCV RNA Level
Negative HCV RNA by blood testing at 12 weeks after the last dose of treatment.
Time frame: 12 weeks post last dose of treatment with DAA
Population: Number of subjects completing full course of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment With Direct Acting Antiviral for HCV | Undetectable Blood HCV RNA Level | 15 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events
Safety and tolerability of DAA therapy in the lung transplant recipient monitored by quantifying the number of treatment related adverese events per patient and evaluation clinically significant out of range lab results as compared to baseline/pretreatment values per patient
Time frame: 8 weeks
Population: Number of participants receiving at least 1 dose of DAA treatment were included in the analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment With Direct Acting Antiviral for HCV | Number of Participants With Treatment Emergent Adverse Events | 0 Participants |
Secondary
Tolerability (Based on Number of Adverse Events and Clinically Significant Laboratory Values)
Tolerability of commercially available DAA therapy in the lung transplant patient will be monitored by quantifying the number of treatment related adverse events per patient and evaluating clinically significant laboratory results
Time frame: 8 weeks
Population: Number of participants receiving at least one dose of DAA were included in the analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment With Direct Acting Antiviral for HCV | Tolerability (Based on Number of Adverse Events and Clinically Significant Laboratory Values) | 0 Participants |