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Trial record 61 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

Impact of Hepatitis C Therapy and Bone Health (HCV)

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: NCT03221582
Recruitment Status : Terminated (Site unable to recruit the agreed upon number of participants)
First Posted : July 18, 2017
Last Update Posted : August 19, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Dallas VA Medical Center

Brief 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.

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Hepatitis C Drug: EBR/GZR Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Impact of HCV Therapy on Cardiovascular Risk and Bone Health
Actual Study Start Date : August 28, 2017
Actual Primary Completion Date : November 26, 2018
Actual Study Completion Date : November 30, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: EBR/GZR (Zepatier) - HCV/HIV co-infected
Drug: Elbasvir (EBR) 50 mg and Grazoprevir (GZR) 100 mg single tablet by mouth, once daily.
Drug: EBR/GZR
Elbasvir and Grazoprevir (EBR/GZR) tablet by mouth, once daily.
Other Name: Zepatier

Experimental: EBR/GZR (Zepatier) - HCV monoinfected
Drug: Elbasvir (EBR) 50 mg and Grazoprevir (GZR) 100 mg single tablet by mouth, once daily.
Drug: EBR/GZR
Elbasvir and Grazoprevir (EBR/GZR) tablet by mouth, once daily.
Other Name: Zepatier




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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. ]
    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).

  2. 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 ]
    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).

  3. 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. ]
    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).

  4. 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. ]
    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).

  5. 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. ]
    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).

  6. 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. ]
    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).

  7. 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 ]
    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).

  8. 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. ]
    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).

  9. 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. ]
    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).

  10. 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. ]
    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).



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. HCV antibody and HCV RNA positive
  2. HCV Genotype 1a, 1b, or 4
  3. Liver staging assessment:

    a. 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

  4. 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:

    1. raltegravir
    2. dolutegravir
    3. 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

Exclusion Criteria:

  1. Hepatitis B surface antigen positivity
  2. Decompensated cirrhosis (Child Pugh B or C)
  3. Any prior hepatitis C treatment
  4. Pregnant or nursing
  5. Treatment with any medication specifically contraindicated with EBR/GZR or not recommended for concomitant use as per the prescribing label (Table 2)
  6. Age less than 18
  7. Prisoners or subjects otherwise involuntarily incarcerated
  8. Absence of signed informed consent by patient or appropriate surrogate
  9. Known hypersensitivity to elbasvir or grazoprevir
  10. For patients with genotype 1a, one more of the following mutations on baseline NS5A genotype: M28, Q30, L31, or Y93

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03221582


Locations
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United States, Texas
Dallas VA Medical Center
Dallas, Texas, United States, 75216
Sponsors and Collaborators
Dallas VA Medical Center
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Roger Bedimo, MD Dallas VAMC

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Responsible Party: Dallas VA Medical Center
ClinicalTrials.gov Identifier: NCT03221582    
Other Study ID Numbers: MISP 54850
First Posted: July 18, 2017    Key Record Dates
Last Update Posted: August 19, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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MK-5172
Elbasvir-grazoprevir drug combination
Hepatitis C
Acquired Immunodeficiency Syndrome
HIV Infections
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
RNA Virus Infections
Flaviviridae Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Antiviral Agents
Anti-Infective Agents