HCV CoinfectionRIBACOPNCT02505243
Evaluation of RIBAvirin Plasma COncentrations in Patients With Chronic Hepatitis C Infection Routinely Treated With Modern DAA Regimens
An observational study of HCV Coinfection and Hepatitis C, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
The aim of this study is to evaluate RBV plasma concentrations when used in combination with newly developed DAA combinations. If possible, its correlations with SVR rates and incidence of anaemia will be assessed in HCV-patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HCV Coinfection, Hepatitis C
- How many people
- 252 participants
- Where
- 1 siteNetherlands
- Study dates
- Jun 2015to Jun 2016
- Phase
- Observational
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: chronicHCV infected patients treated with direct acting antivirals (daclatasvir, simeprevir, sofosbuvir, paritaprevir, ombitasvir, dasabuvir, ledipasvir) and ribavirin.
Who may be able to join
- HCV-infected patients
- Patient must be treated with ribavirin. The dosage of ribavirin may vary, as the different centers have different protocols for RBV dosing.
- Patient must be treated with one or more DAAs (simeprevir, sofosbuvir, daclatasvir, ledipasvir, paritaprevir, ombitasvir, or dasabuvir).
- At least 18 years of age at start of treatment.
Who cannot join
- None
Trial locations and contacts
1 site in 1 country.
About this study
The aim of this study is to evaluate RBV plasma concentrations when used in combination with newly developed DAA combinations. If possible, its correlations with SVR rates and incidence of anaemia will be assessed in HCV-patients.
Read the detailed description
Ribavirin (RBV) is a synthetic guanosine analogue that is used to treat patients infected with hepatitis C virus (HCV). For many years, RBV has been the cornerstone of the HCV treatment in combination with peg interferon (PEG-IFN). Since the development of direct-acting antivirals (DAA), PEG-IFN free treatment regimes became first choice of HCV treatment in the Netherlands. RBV still plays an important role in some of these regimens. The European Association for the Study of the liver (EASL) included RBV in PEG-IFN free regimens in combination with sofosbuvir, simeprevir and daclatasvir for HCV genotype (GT) 1, 3 and 4. Patients with predictors of poor response are candidates for DAA therapy combined with RBV, for instance prior null responders and/or patients with cirrhosis. For the treatment of genotype 2 (GT2) and 3 RBV is used in combination with sofosbuvir.
Chronic HCV infection is treated with combination therapy, therefore manufacturers developed combination tablets such as Gilead's Harvoni (ledipasvir + sofosbuvir) and Abbvie's 3D combination (paritaprevir, ombitasvir, dasabuvir and ritonavir). Possibly, RBV will be added to these regimes in the future when the patient is a prior null responder or suffering from cirrhosis.
As RBV is a guanine analogue it is not specific for HCV and some severe adverse effects are known. The most important adverse effect is haemolytic anaemia,which usually occurs during the first weeks of treatment (>10% of the treated patients, depending on co-medication). Other adverse reactions that were frequently reported were: neutropenia, anorexia, depression/insomnia, headache, dizziness, dyspnea, and cough 5.
In dual (PEG-IFN + RBV) HCV therapy RBV concentrations were associated with efficacy and toxicity. Also in former studies in HCV-infected patients treated with telaprevir (TVR) or boceprevir (BOC) in combination with PEG-IFN, the plasma concentration of RBV was associated with Sustained Virologic Response (SVR) and anaemia (defined as Hb<8,5 g/dL). We have tried to determine an optimal therapeutic range for RBV when combined with these DAAs. The plasma concentration of RBV at week 8 should be 2.2-5.3 mg/L in combination with TVR. 48% of the HCV patients in the cohort had these plasma concentrations of which 81% achieved SVR and 5.2% reported anaemia. In combination with BOC the plasma concentration should be 2.2-3.6 mg/L, 50% of patients had these concentrations. In this group 69% of patients achieved SVR and 46% anaemia. So, for these therapies, therapeutic ranges for RBV could be defined for the optimal SVR rates and the lowest incidence of anaemia 6, 7.
As TVR and BOC have now been replaced by novel DAAs, we would like to investigate this described relationship between RBV concentrations, SVR and anaemia also with the newer DAAs that were licensed in the last year (simeprevir and sofosbuvir) and that are going to be available in 2015 in The Netherlands (daclatasvir, Harvoni, Abbvie 3D combo).
The aim of this study is to evaluate RBV plasma concentrations when used in combination with newly developed DAA combinations. If possible, its correlations with SVR rates and incidence of anaemia will be assessed in HCV-patients.
- Conditions
- HCV Coinfection, Hepatitis C
- Keywords
- ribavirin, direct-acting antivirals, pharmacokinetics, therapeutic drug monitoring
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| HCV patients | HCV patients treated with direct acting antivirals and ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ribavirin concentration
Analysis ribavirin concentration in plasma
Measured: Ribavirin concentraition at week 8 of treatment
Secondary outcomes (3)
Sustained virological response (SVR12)
HCV RNA analysis in plasma
Measured: Change from baseline virological resonse, 12 weeks after treatment.
Hemoglobin concentrations
Analysis Hb plasma concentration
Measured: Change from baseline hemoglobin concentrationes, 8 weeks after treatment.
Ribavirin concentration
Analysis ribavirin concentrations in plasma
Measured: Ribavirin concentraition at week 2 of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2015 (estimated)
- Study startJun 2015
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HCV CoinfectionStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 252 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Erasmus Medical Center, University Medical Center Groningen, UMC Utrecht, Maastricht University Medical Center
- Responsible party
- Sponsor
- Investigators
- David Burder, PharmdD, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02505243
- Sponsor's protocol ID
- UMCN-AKF-15.03
- Acronym
- RIBACOP
- Status last verified
- Dec 2020
- First submitted
- 15 Jul 2015
- Last updated
- 7 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
van Tilborg M, Lieveld FI, Smolders EJ, van Erpecum KJ, de Kanter CTMM, Maan R, van der Valk M, Arends JE, Dofferhoff ASM, Blokzijl H, Bijmolen M, Drenth JPH, de Knegt RJ, Burger DM; HepNed Study Group. Ribavirin steady-state plasma level is a predictor of sustained virological response in hepatitis C-infected patients treated with direct-acting antivirals. Aliment Pharmacol Ther. 2017 Nov;46(9):864-872. doi: 10.1111/apt.14288. Epub 2017 Sep 7.
PubMed 28881031
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of RIBAvirin Plasma COncentrations in Patients With Chronic Hepatitis C Infection Routinely Treated With Modern DAA Regimens
- ClinicalTrials.gov ID
- NCT02505243
- Acronym / sponsor ID
- RIBACOP / UMCN-AKF-15.03
- Conditions
- HCV Coinfection, Hepatitis C
- Keywords
- ribavirin, direct-acting antivirals, pharmacokinetics, therapeutic drug monitoring
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 252 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Erasmus Medical Center, University Medical Center Groningen, UMC Utrecht, Maastricht University Medical Center
- Study start
- Jun 2015
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 22 Jul 2015 (estimated)
- 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.
The aim of this study is to evaluate RBV plasma concentrations when used in combination with newly developed DAA combinations. If possible, its correlations with SVR rates and incidence of anaemia will be assessed in HCV-patients.
Detailed description
Ribavirin (RBV) is a synthetic guanosine analogue that is used to treat patients infected with hepatitis C virus (HCV). For many years, RBV has been the cornerstone of the HCV treatment in combination with peg interferon (PEG-IFN). Since the development of direct-acting antivirals (DAA), PEG-IFN free treatment regimes became first choice of HCV treatment in the Netherlands. RBV still plays an important role in some of these regimens. The European Association for the Study of the liver (EASL) included RBV in PEG-IFN free regimens in combination with sofosbuvir, simeprevir and daclatasvir for HCV genotype (GT) 1, 3 and 4. Patients with predictors of poor response are candidates for DAA therapy combined with RBV, for instance prior null responders and/or patients with cirrhosis. For the treatment of genotype 2 (GT2) and 3 RBV is used in combination with sofosbuvir.
Chronic HCV infection is treated with combination therapy, therefore manufacturers developed combination tablets such as Gilead's Harvoni (ledipasvir + sofosbuvir) and Abbvie's 3D combination (paritaprevir, ombitasvir, dasabuvir and ritonavir). Possibly, RBV will be added to these regimes in the future when the patient is a prior null responder or suffering from cirrhosis.
As RBV is a guanine analogue it is not specific for HCV and some severe adverse effects are known. The most important adverse effect is haemolytic anaemia,which usually occurs during the first weeks of treatment (>10% of the treated patients, depending on co-medication). Other adverse reactions that were frequently reported were: neutropenia, anorexia, depression/insomnia, headache, dizziness, dyspnea, and cough 5.
In dual (PEG-IFN + RBV) HCV therapy RBV concentrations were associated with efficacy and toxicity. Also in former studies in HCV-infected patients treated with telaprevir (TVR) or boceprevir (BOC) in combination with PEG-IFN, the plasma concentration of RBV was associated with Sustained Virologic Response (SVR) and anaemia (defined as Hb<8,5 g/dL). We have tried to determine an optimal therapeutic range for RBV when combined with these DAAs. The plasma concentration of RBV at week 8 should be 2.2-5.3 mg/L in combination with TVR. 48% of the HCV patients in the cohort had these plasma concentrations of which 81% achieved SVR and 5.2% reported anaemia. In combination with BOC the plasma concentration should be 2.2-3.6 mg/L, 50% of patients had these concentrations. In this group 69% of patients achieved SVR and 46% anaemia. So, for these therapies, therapeutic ranges for RBV could be defined for the optimal SVR rates and the lowest incidence of anaemia 6, 7.
As TVR and BOC have now been replaced by novel DAAs, we would like to investigate this described relationship between RBV concentrations, SVR and anaemia also with the newer DAAs that were licensed in the last year (simeprevir and sofosbuvir) and that are going to be available in 2015 in The Netherlands (daclatasvir, Harvoni, Abbvie 3D combo).
The aim of this study is to evaluate RBV plasma concentrations when used in combination with newly developed DAA combinations. If possible, its correlations with SVR rates and incidence of anaemia will be assessed in HCV-patients.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HCV patients | – | –HCV patients treated with direct acting antivirals and ribavirin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- chronicHCV infected patients treated with direct acting antivirals (daclatasvir, simeprevir, sofosbuvir, paritaprevir, ombitasvir, dasabuvir, ledipasvir) and ribavirin.
Key inclusion criteria (4 listed)
- HCV-infected patients
- Patient must be treated with ribavirin. The dosage of ribavirin may vary, as the different centers have different protocols for RBV dosing.
- Patient must be treated with one or more DAAs (simeprevir, sofosbuvir, daclatasvir, ledipasvir, paritaprevir, ombitasvir, or dasabuvir).
- At least 18 years of age at start of treatment.
Key exclusion criteria (1 listed)
- None
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Ribavirin concentration
Time frame: Ribavirin concentraition at week 8 of treatment
Analysis ribavirin concentration in plasma
3 secondary outcomes
Sustained virological response (SVR12)
Time frame: Change from baseline virological resonse, 12 weeks after treatment.
Hemoglobin concentrations
Time frame: Change from baseline hemoglobin concentrationes, 8 weeks after treatment.
Ribavirin concentration
Time frame: Ribavirin concentraition at week 2 of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2020.
- Results publication: PubMed 28881031van Tilborg M, Lieveld FI, Smolders EJ, van Erpecum KJ, de Kanter CTMM, Maan R, van der Valk M, Arends JE, Dofferhoff ASM, Blokzijl H, Bijmolen M, Drenth JPH, de Knegt RJ, Burger DM; HepNed Study Group. Ribavirin steady-state plasma level is a predictor of sustained virological response in hepatitis C-infected patients treated with direct-acting antivirals. Aliment Pharmacol Ther. 2017 Nov;46(9):864-872. doi: 10.1111/apt.14288. Epub 2017 Sep 7.
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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.
David Burder, PharmdD, PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HCV Coinfection and Hepatitis C, run by Radboud University Medical Center at 1 site in Netherlands.
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 4 inclusion and 1 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: finished, as of the sponsor's last update on 7 Dec 2020. 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 Netherlands. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Ribavirin concentration (time frame: Ribavirin concentraition at week 8 of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02505243, which also lists 1 linked publication.
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 7 Dec 2020; AzTrials last refreshed its copy on 7 Nov 2026.