Human Immunodeficiency VirusPhase 4HCVNCT03221582
Impact of Hepatitis C Therapy and Bone Health
A Phase 4 study testing EBR/GZR in people with Human Immunodeficiency Virus and Hepatitis C, run by Dallas VA Medical Center at 1 site in United States.
Trial summary
An evaluation of the impact of Elbasvir and Grazoprevir (EBR/GZR) HCV therapy on the heart risk and bone health of HCV mono-infected and HIV/HCV co-infected patients. Read more about this study
- Who is it for?
- Ages 40 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Human Immunodeficiency Virus, Hepatitis C
- What is being tested?
- EBR/GZR
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Aug 2017to 30 Nov 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- HCV antibody and HCV RNA positive
- HCV Genotype 1a, 1b, or 4
- Liver staging assessment:
- Cirrhosis will be defined by any of the following: i. A liver biopsy prior to day 1 of this study showing cirrhosis (F4) ii. Fibroscan within 12 calendar months of day 1 of this study showing cirrhosis with result > 12.5 kPa iii. FibroSURE performed during screening with a score > 0.75 and APRI > 2 b. Absence of cirrhosis will be defined by any of the following: i. Liver biopsy performed within 24 months of day 1 of this study showing absence of cirrhosis ii. Fibroscan performed within 12 months of day 1 of this study with a result of ≤ 12.5 kPa iii. FibroSURE score ≤ 0.48 and APRI ≤ 1 during screening
- If HIV co-infected, HAART regimen will consist of two NRTIs (abacavir, tenofovir disoproxil fumarate or tenofovir alafenamide, each in combination with lamivudine or emtricitabine) with one of the following 3rd agents:
- raltegravir
- dolutegravir
- rilpivirine HIV co-infected patients must be on their stable HAART regimen for at least 6 months, with HIV viral load < 50 c/mL at screening
Who cannot join
- Hepatitis B surface antigen positivity
- Decompensated cirrhosis (Child Pugh B or C)
- Any prior hepatitis C treatment
- Pregnant or nursing
- Treatment with any medication specifically contraindicated with EBR/GZR or not recommended for concomitant use as per the prescribing label (Table 2)
- Age less than 18
Show all 10Show fewer
- Prisoners or subjects otherwise involuntarily incarcerated
- Absence of signed informed consent by patient or appropriate surrogate
- Known hypersensitivity to elbasvir or grazoprevir
- For patients with genotype 1a, one more of the following mutations on baseline NS5A genotype: M28, Q30, L31, or Y93
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of HCV Therapy on Cardiovascular Risk and Bone Health
An evaluation of the impact of Elbasvir and Grazoprevir (EBR/GZR) HCV therapy on the heart risk and bone health of HCV mono-infected and HIV/HCV co-infected patients.
Read the detailed description
Both HCV and HIV are associated with an increased risk of osteoporosis and osteoporotic fractures among HIV-infected patients and the general population. While HIV significantly increases cardiovascular risk, the contribution of HCV to cardiovascular disease (CVD) is less certain. Increased inflammation could potentially underlie the effect of HCV on CVD, bone health, and other extra-hepatic complications. HCV appears to remain an independent predictor of osteoporotic fractures even after controlling for severity of liver disease. The impact of HCV therapy on inflammation, CVD and bone health is unclear. Our previous studies suggest a beneficial impact of interferon therapy on bone turnover and some CVD markers, while others studies have found on-treatment increases in bone mineral density with interferon-based therapy. Whether these are related to the interferon itself or the virologic response, and whether changes in biomarkers lead to improved fracture risk or CVD morbidity is uncertain. Investigator propose to conduct a prospective analysis of markers of inflammation, immune activation, and bone turnover as well as bone mineral density (BMD) among both HIV/HCV co-infected and HCV mono-infected patients undergoing treatment with the novel direct-acting antiviral elbasvir/grazoprevir (EBR/GZR). Should EBR/GZR therapy significantly improve CV risk and bone health, it would be an additional benefit and indication for its use in HCV therapy.
- Conditions
- Human Immunodeficiency Virus, Hepatitis C
- Being tested
- EBR/GZR
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EBR/GZRDrug
Also called Zepatier
Elbasvir and Grazoprevir (EBR/GZR) tablet by mouth, once daily.
| Study group | Role | What they receive |
|---|---|---|
| EBR/GZR (Zepatier) - HCV/HIV co-infected | Experimental | Drug: Elbasvir (EBR) 50 mg and Grazoprevir (GZR) 100 mg single tablet by mouth, once daily. Receives: Drug: EBR/GZR |
| EBR/GZR (Zepatier) - HCV monoinfected | Experimental | Drug: Elbasvir (EBR) 50 mg and Grazoprevir (GZR) 100 mg single tablet by mouth, once daily. Receives: Drug: EBR/GZR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients and HIV/HCV co-infected patients
Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, positron emission tomography (PET) scanning for arterial inflammation, coronary calcification and myocardial viability.
Measured: 48 weeks
Secondary outcomes (10)
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients.
Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by dual energy x-ray absorptiometry (DXA) scan and trabecular bone score (TBS).
Measured: Biomarkers of inflammation and bone turnover measured at week 0 of therapy.
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients.
Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
Measured: Bone mineral density measured at week 0 of therapy
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients.
Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
Measured: Biomarkers of inflammation and bone turnover measured at week 12 of therapy.
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients.
Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
Measured: Biomarkers of inflammation and bone turnover measured at week 24 of therapy.
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients.
Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
Measured: Bone mineral density measured at week 48 of therapy.
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients.
Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
Measured: Biomarkers of inflammation and bone turnover measured at week 0 of therapy.
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients.
Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
Measured: Bone mineral density measured at week 0 of therapy
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients.
Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
Measured: Biomarkers of inflammation and bone turnover measured at week 12 of therapy.
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients.
Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
Measured: Biomarkers of inflammation and bone turnover measured at week 24 of therapy.
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients.
Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, PET scanning for arterial inflammation, coronary calcification and myocardial viability. Bone health will be assessed by serological markers of bone turnover and bone mineral density (BMD) by DXA scan and trabecular bone score (TBS).
Measured: Biomarkers of inflammation and bone turnover measured at week 48 of therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2017
- Study start28 Aug 2017
- Primary completion26 Nov 2018
- Study completion30 Nov 2018
Why it stopped: Site unable to recruit the agreed upon number of participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Human Immunodeficiency VirusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dallas VA Medical Center
- Sponsor type
- US federal agency
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Roger Bedimo, MD, Principal investigator, Dallas VAMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03221582
- Sponsor's protocol ID
- MISP 54850
- Acronym
- HCV
- Status last verified
- Aug 2019
- First submitted
- 27 Jun 2017
- Last updated
- 19 Aug 2019
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of HCV Therapy on Cardiovascular Risk and Bone Health
- ClinicalTrials.gov ID
- NCT03221582
- Acronym / sponsor ID
- HCV / MISP 54850
- Conditions
- Human Immunodeficiency Virus, Hepatitis C
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Site unable to recruit the agreed upon number of participants
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Dallas VA Medical CenterUS federal agency
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 28 Aug 2017 (actual)
- Primary completion
- 26 Nov 2018 (actual)
- Study completion
- 30 Nov 2018 (actual)
- First posted
- 18 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An evaluation of the impact of Elbasvir and Grazoprevir (EBR/GZR) HCV therapy on the heart risk and bone health of HCV mono-infected and HIV/HCV co-infected patients.
Detailed description
Both HCV and HIV are associated with an increased risk of osteoporosis and osteoporotic fractures among HIV-infected patients and the general population. While HIV significantly increases cardiovascular risk, the contribution of HCV to cardiovascular disease (CVD) is less certain. Increased inflammation could potentially underlie the effect of HCV on CVD, bone health, and other extra-hepatic complications. HCV appears to remain an independent predictor of osteoporotic fractures even after controlling for severity of liver disease. The impact of HCV therapy on inflammation, CVD and bone health is unclear. Our previous studies suggest a beneficial impact of interferon therapy on bone turnover and some CVD markers, while others studies have found on-treatment increases in bone mineral density with interferon-based therapy. Whether these are related to the interferon itself or the virologic response, and whether changes in biomarkers lead to improved fracture risk or CVD morbidity is uncertain. Investigator propose to conduct a prospective analysis of markers of inflammation, immune activation, and bone turnover as well as bone mineral density (BMD) among both HIV/HCV co-infected and HCV mono-infected patients undergoing treatment with the novel direct-acting antiviral elbasvir/grazoprevir (EBR/GZR). Should EBR/GZR therapy significantly improve CV risk and bone health, it would be an additional benefit and indication for its use in HCV therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EBR/GZR (Zepatier) - HCV/HIV co-infected | Experimental | Drug: EBR/GZRDrug: Elbasvir (EBR) 50 mg and Grazoprevir (GZR) 100 mg single tablet by mouth, once daily. |
| EBR/GZR (Zepatier) - HCV monoinfected | Experimental | Drug: EBR/GZRDrug: Elbasvir (EBR) 50 mg and Grazoprevir (GZR) 100 mg single tablet by mouth, once daily. |
Who may qualify
- Ages
- 40 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- HCV antibody and HCV RNA positive
- HCV Genotype 1a, 1b, or 4
- Liver staging assessment:
- If HIV co-infected, HAART regimen will consist of two NRTIs (abacavir, tenofovir disoproxil fumarate or tenofovir alafenamide, each in combination with lamivudine or emtricitabine) with one of the following 3rd agents:
Key exclusion criteria (10 listed)
- Hepatitis B surface antigen positivity
- Decompensated cirrhosis (Child Pugh B or C)
- Any prior hepatitis C treatment
- Pregnant or nursing
- Treatment with any medication specifically contraindicated with EBR/GZR or not recommended for concomitant use as per the prescribing label (Table 2)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EBR/GZRAlso: ZepatierElbasvir and Grazoprevir (EBR/GZR) tablet by mouth, once daily. | Drug | EBR/GZR (Zepatier) - HCV monoinfected, EBR/GZR (Zepatier) - HCV/HIV co-infected |
Primary outcome
Evaluate the impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients and HIV/HCV co-infected patients
Time frame: 48 weeks
Cardiovascular health will be assessed by serologic markers of inflammation; in addition to, positron emission tomography (PET) scanning for arterial inflammation, coronary calcification and myocardial viability.
10 secondary outcomes
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients.
Time frame: Biomarkers of inflammation and bone turnover measured at week 0 of therapy.
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients.
Time frame: Bone mineral density measured at week 0 of therapy
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients.
Time frame: Biomarkers of inflammation and bone turnover measured at week 12 of therapy.
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients.
Time frame: Biomarkers of inflammation and bone turnover measured at week 24 of therapy.
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients.
Time frame: Bone mineral density measured at week 48 of therapy.
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients.
Time frame: Biomarkers of inflammation and bone turnover measured at week 0 of therapy.
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients.
Time frame: Bone mineral density measured at week 0 of therapy
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients.
Time frame: Biomarkers of inflammation and bone turnover measured at week 12 of therapy.
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients.
Time frame: Biomarkers of inflammation and bone turnover measured at week 24 of therapy.
Impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HIV/HCV co-infected patients.
Time frame: Biomarkers of inflammation and bone turnover measured at week 48 of therapy.
Results and safety
The study was stopped early (reason given: Site unable to recruit the agreed upon number of participants). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roger Bedimo, MD principal investigator
Dallas VAMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing EBR/GZR in people with Human Immunodeficiency Virus and Hepatitis C, run by Dallas VA Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Site unable to recruit the agreed upon number of participants). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the impact of EBR/GZR HCV therapy on the cardiovascular risk and bone health of HCV mono-infected patients and HIV/HCV co-infected patients (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2019.