Study of Hepatitis Eradication Receiving Protease Inhibitor Administration
| Status: | Recruiting |
|---|---|
| Conditions: | Peripheral Vascular Disease, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/24/2019 |
| Start Date: | March 20, 2019 |
| End Date: | March 31, 2023 |
| Contact: | David Baran, MD |
| Email: | dabaran@sentara.com |
| Phone: | 7573882831 |
The Study of Hepatitis Eradication Receiving Protease Inhibitor Administration
This is a prospective, non-blinded cohort study that will assess the safety, tolerability,
and antiviral efficacy of glecaprevir/pibrentasivir therapy given post-discharge to
HCV-negative recipients of HCV infected donors. Patients who meet entry criteria will be
enrolled while on the transplant waitlist. At the time of transplant, some donors will be HCV
positive / NAT positive and some will not be infected. Enrolled patients who receive an HCV
negative donor will serve as contemporaneous controls. All study subjects who receive an HCV
positive organ will be confirmed to have acquired HCV infection and genotype will be assessed
prior to treatment with therapy.
and antiviral efficacy of glecaprevir/pibrentasivir therapy given post-discharge to
HCV-negative recipients of HCV infected donors. Patients who meet entry criteria will be
enrolled while on the transplant waitlist. At the time of transplant, some donors will be HCV
positive / NAT positive and some will not be infected. Enrolled patients who receive an HCV
negative donor will serve as contemporaneous controls. All study subjects who receive an HCV
positive organ will be confirmed to have acquired HCV infection and genotype will be assessed
prior to treatment with therapy.
4. STUDY PROCEDURES 4.1 Subject Enrollment The patient is considered to be enrolled when they
sign study consent. This may be months or years prior to the date of transplantation and
therefore all study patients will be asked to affirm consent at the time of transplantation.
There are 2 non-randomized study groups: Those patients who receive a non-HCV donor and those
who receive a donor with HCV infection. Subjects will re-sign the consent on the line
reserved for this purpose at the time of the transplant.
If the patient presented with a hepatitis C donor heart decides not to take that heart, they
would remain in the study and when a suitable heart is found (infected or not), they would be
followed post-transplant in the study.
4.2 Study Procedures Following transplantation with an HCV infectious donor, HCV viral load
(RNA assay) will be measured at days 3,7 and 14 days post-transplant. The HCV viral load
assay is a routine FDA cleared laboratory test which is one of the standard labs available at
Sentara Norfolk General Hospital. It involves a blood sample of 5 cc which is then processed
in the lab. Based on prior work, it is likely that all transplant recipients with infectious
donors will seroconvert within this time frame. If these patients remain negative for HCV
RNA, it will be rechecked every month for a total of 6 months. This routine testing is
covered by insurance as this is the clinical standard for donors with elevated risk (Public
Health Service increased risk).
Once a patient seroconverts to HCV positive, insurance authorization for treatment will be
sought for treatment with glecaprevir/pibrentasivir. Based on input from Dr. Michael Ryan of
Gastroenterology, insurance carriers are approving therapy given the noted efficacy, low
comparative cost and the recent FDA approval of this drug in renal and liver transplant
recipients. If insurance denies this cost, the medication will be provided by the Hospital at
no charge to the patient, given the poor long-term outcome of HCV untreated.
The study treatment is oral glecaprevir/pibrentasivir, 3 tablets daily with food, for a total
of 12 weeks. The medication will be paid by the patient's insurance prescription coverage.
Serial measurements of HCV NAT (every month) will be conducted including through 24 weeks
post-transplant. In addition, coronary angiography plus coronary intravascular ultrasound
will be conducted at 6-12 weeks post-transplant and at one-year post transplant which will
allow careful evaluation for cardiac allograft vasculopathy. Of note, it has been the policy
of the Sentara Heart Transplant program for more than 5 years to perform baseline (early
post-transplant) and annual coronary angiography and coronary intravascular ultrasound, and
regardless of study participation, all patients will undergo this standard of care
surveillance.
Post-transplant standard of care visits include frequent routine clinic labs (comprehensive
metabolic panel, hepatic function panel, CMV viral load by PCR, creatinine kinase, complete
blood count, B-type natriuretic peptide (BNP), tacrolimus or cyclosporine level if
appropriate, sirolimus level if appropriate.
4.3 Post-Treatment Assessments Patients will have clinical standard of care visits to the
transplant clinic, typically monthly in the first 6 months following transplantation. HCV NAT
testing will be obtained at each visit for patients who received an infected donor, along
with standard of care testing including cardiac biopsies, echocardiograms, chest-x-rays and
other needed assessments. NAT testing is standard of care for recipients of increased
infectious risk donors.
A visit will be mandatory at 12 weeks following the last dose of glecaprevir/pibrentasivir to
draw HCV NAT testing.
Failure of HCV treatment If HCV RNA ≥ LLOQ at end of treatment (12 weeks of therapy) or viral
relapse occurs in the Post-treatment follow-up, consultation with infectious disease and
hepatology will be obtained. Testing for HCV drug resistance will be performed and patient
will be treated as clinically indicated by the AHF team in consultation with specialists.
Patients will be followed in regard to outcomes and achievement of SVR-12 until this occurs,
or the patient dies or otherwise withdraws from the study.
4.4 End of Study Subjects are considered to have completed the study at 1 year
post-transplant or the 1 year cardiac catheterization / IVUS is conducted, whichever is
later.
sign study consent. This may be months or years prior to the date of transplantation and
therefore all study patients will be asked to affirm consent at the time of transplantation.
There are 2 non-randomized study groups: Those patients who receive a non-HCV donor and those
who receive a donor with HCV infection. Subjects will re-sign the consent on the line
reserved for this purpose at the time of the transplant.
If the patient presented with a hepatitis C donor heart decides not to take that heart, they
would remain in the study and when a suitable heart is found (infected or not), they would be
followed post-transplant in the study.
4.2 Study Procedures Following transplantation with an HCV infectious donor, HCV viral load
(RNA assay) will be measured at days 3,7 and 14 days post-transplant. The HCV viral load
assay is a routine FDA cleared laboratory test which is one of the standard labs available at
Sentara Norfolk General Hospital. It involves a blood sample of 5 cc which is then processed
in the lab. Based on prior work, it is likely that all transplant recipients with infectious
donors will seroconvert within this time frame. If these patients remain negative for HCV
RNA, it will be rechecked every month for a total of 6 months. This routine testing is
covered by insurance as this is the clinical standard for donors with elevated risk (Public
Health Service increased risk).
Once a patient seroconverts to HCV positive, insurance authorization for treatment will be
sought for treatment with glecaprevir/pibrentasivir. Based on input from Dr. Michael Ryan of
Gastroenterology, insurance carriers are approving therapy given the noted efficacy, low
comparative cost and the recent FDA approval of this drug in renal and liver transplant
recipients. If insurance denies this cost, the medication will be provided by the Hospital at
no charge to the patient, given the poor long-term outcome of HCV untreated.
The study treatment is oral glecaprevir/pibrentasivir, 3 tablets daily with food, for a total
of 12 weeks. The medication will be paid by the patient's insurance prescription coverage.
Serial measurements of HCV NAT (every month) will be conducted including through 24 weeks
post-transplant. In addition, coronary angiography plus coronary intravascular ultrasound
will be conducted at 6-12 weeks post-transplant and at one-year post transplant which will
allow careful evaluation for cardiac allograft vasculopathy. Of note, it has been the policy
of the Sentara Heart Transplant program for more than 5 years to perform baseline (early
post-transplant) and annual coronary angiography and coronary intravascular ultrasound, and
regardless of study participation, all patients will undergo this standard of care
surveillance.
Post-transplant standard of care visits include frequent routine clinic labs (comprehensive
metabolic panel, hepatic function panel, CMV viral load by PCR, creatinine kinase, complete
blood count, B-type natriuretic peptide (BNP), tacrolimus or cyclosporine level if
appropriate, sirolimus level if appropriate.
4.3 Post-Treatment Assessments Patients will have clinical standard of care visits to the
transplant clinic, typically monthly in the first 6 months following transplantation. HCV NAT
testing will be obtained at each visit for patients who received an infected donor, along
with standard of care testing including cardiac biopsies, echocardiograms, chest-x-rays and
other needed assessments. NAT testing is standard of care for recipients of increased
infectious risk donors.
A visit will be mandatory at 12 weeks following the last dose of glecaprevir/pibrentasivir to
draw HCV NAT testing.
Failure of HCV treatment If HCV RNA ≥ LLOQ at end of treatment (12 weeks of therapy) or viral
relapse occurs in the Post-treatment follow-up, consultation with infectious disease and
hepatology will be obtained. Testing for HCV drug resistance will be performed and patient
will be treated as clinically indicated by the AHF team in consultation with specialists.
Patients will be followed in regard to outcomes and achievement of SVR-12 until this occurs,
or the patient dies or otherwise withdraws from the study.
4.4 End of Study Subjects are considered to have completed the study at 1 year
post-transplant or the 1 year cardiac catheterization / IVUS is conducted, whichever is
later.
Inclusion Criteria:
- Subjects must meet all of the inclusion criteria specified below in order to be
eligible for participation in this study
1. Willing and capable of providing written informed consent
2. Age ≥18 years
3. On UNOS list as a candidate for heart transplant
Exclusion Criteria:
- Subjects who meet any of the following exclusion criteria cannot be enrolled in this
study.
1. Individuals under 18 years of age
2. History of advanced liver disease, including active hepatitis B or C, detectable
hepatitis B surface Ag, hepatitis B DNA, HCV RNA, or cirrhosis
3. Pregnant individuals
4. HIV antibody positive
We found this trial at
1
site
600 Gresham Dr
Norfolk, Virginia 23507
Norfolk, Virginia 23507
(757) 388-3000
Phone: 757-388-2831
Sentara Norfolk General Hospital Sentara Norfolk General Hospital is recognized as the number one ranked...
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