Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT02505243 |
Other study ID # |
UMCN-AKF-15.03 |
Secondary ID |
|
Status |
Completed |
Phase |
|
First received |
|
Last updated |
|
Start date |
June 2015 |
Est. completion date |
June 2016 |
Study information
Verified date |
December 2020 |
Source |
Radboud University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical 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.
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.