Chronic Hepatitis CPhase 4NCT02638233
Therapy With Ledipasvir/Sofosbuvir in Patients With Genotype 1 HCV Infection Receiving Opiate Substitution Therapy
A Phase 4 study testing Sofosbuvir 400mg / Ledipasvir 90 mg (FDC) in people with Chronic Hepatitis C, run by Wilhelminenspital Vienna at 1 site in Austria.
Trial summary
Patients with chronic hepatitis C that are under opiate substitution therapy are likely to have psychiatric comorbidities such as depression; hence an Interferon based therapy is contraindicated. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- Sofosbuvir 400mg / Ledipasvir 90 mg (FDC)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteAustria
- Study dates
- Sep 2015to Sep 2016
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic genotype 1 HCV infection
- Fibrosis F0-F3 (i.e. non-cirrhotic confirmed by Fibroscan <12.5kPa)
- Stable opiate substitution therapy
- Regular visits at the low threshold facility during the last month
Who cannot join
- Lack or unwillingness of safe contraception, pregnancy
- Liver cirrhosis (Fibroscan ≥12.5kPa)
- Coinfection with HBV (Hepatitis B Virus) or HIV (coinfection with HIV is excluded only because there are very few coinfected patients under care at the "Ambulatorium Suchthilfe Wien" and hence this subpopulation would be very small)
- Severe comorbidities resulting in a life expectancy of less than five years
- HCC (Hepatocellular carcinoma)
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
Wilhelminenspital
Vienna, State of Vienna, 1160
Michael Gschwantler, Prof. MD, 0043 1 491502401, michael.gschwantler@wienkav.at
Johann Haltmayer, MD, HCM, 0043 1 4000 53 603, hans.haltmayer@sd-wien.at
About this study
Official title: Direct Observed Therapy With Ledipasvir/Sofosbuvir in Treatment-naïve Patients With Chronic Genotype 1 HCV (Hepatitis C Virus) Infection Receiving Opiate Substitution Therapy
Patients with chronic hepatitis C that are under opiate substitution therapy are likely to have psychiatric comorbidities such as depression; hence an Interferon based therapy is contraindicated. Additionally many of these patients have a borderline compliance, which makes it impossible to treat them at specialized hepatological centers. An ideal opportunity to treat this patients is treatment with DAAs (Direct Acting Antiviral) which can be administered daily together with the opiate substitution therapy at a low threshold facility.
Read the detailed description
Background:
Patients with active or previous i.v.-drug abuse and patients receiving opiate substitution therapy (OST) represent a major subgroup of the patients with chronic hepatitis C (CHC). Till some years ago it was held, that patients with a history of i.v.-drug abuse and patients receiving OST should not be considered for interferon-based antiviral treatment because of their poor compliance. However, during the past years it became clear, that patients on OST who are considered to be stable by their physicians are good candidates for antiviral therapy. Several studies have shown that SVR (sustained virological response rates) achieved in these patients are similar to results in patients without a history of i.v. drug abuse.
Subgroups of patients receiving OST:Patients receiving OST represent a very heterogeneous population. However, based on empirical observation of the behavior/compliance of each individual patient they can be assigned to one of the following three groups:
Group 1: Patients with very good compliance. These patients do not take drugs anymore and demonstrate a very good compliance. If anti HCV therapy is indicated, these patients can be referred to and treated at a hepatologic Center (i.e. hospital). Such patients have been included in various phase III trials of new direct acting antiviral agents (DAAs).
Group 2: Patients with a very poor compliance. These patients do not keep appointments (regardless whether it is at a low threshold facility or at a hospital). Due to their lack of compliance antiviral therapy of these patients is not feasible.
Group 3: Patients with a borderline compliance. These patients do come to a low threshold facility on a daily basis where they get OST under direct observation of a physician or a nurse. These patients are reluctant to go to specialized hepatitis centers (high inhibition threshold) and hence cannot be treated there. However, anti-HCV treatment can be applied together with OST under direct observation of a physician or a nurse at the low threshold facilities. The "Ambulatorium Suchthilfe Wien" a "low threshold facility" (LTF): The "Ambulatorium Suchthilfe Wien" is a facility that offers medical care to patients with active or former i.v. drug abuse (= (ex-)PWIDs). The medical team at these low-threshold facilities (=LTFs) includes general practitioners, specialists in internal medicine, psychiatrists and nurses. In contrast to hospitals (hepatologic centers in Austria with outpatient clinics in a large hospital), where there is a relatively high "psychological" inhibition threshold for PWIDs with CHC, the LTFs are located in "normal" houses. The setting is such that the "psychological" inhibition threshold for PWIDs to go there is low. At the LTFs (ex-)PWIDs can obtain OST on a daily basis under direct observation of a physician or a nurse. Hence, the patients have a high motivation to come to these facilities daily (to avoid withdrawal symptoms - they do not have a similar incentive/interest/motivation to go to a hospital on a regular basis). The direct observed OST prevents potential selling of medication on the black market. Anti-HCV treatment at the "Ambulatorium Suchthilfe Wien":
Univ.-Prof. Dr. Michael Gschwantler, an experienced hepatologist is cooperating with the "Ambulatorium Suchthilfe Wien" (=LTF). He visits the facility at least once a week (and immediately in the case of any serious problem) and takes care of the patients with regards to hepatitis/liver diseases. Prof. Gschwantler does this voluntarily and unsalaried. He performs routine laboratory and sonographic evaluation of the liver directly at the LTF. Prof. Gschwantler has already treated a small number of eligible "group 3 patients" (patients with borderline compliance as described before) with interferon-based treatment directly at the LTF (patients didn't need to go to a hospital). However, beside compliance issues contraindications against interferon (e.g. due to depression) prevent many (ex-)PWIDs from being treated at the moment.
Study drug:
In this non-interventional study patients with chronic hepatitis C, genotype 1, will be treated with Harvoni® (Sofosbuvir/Ledipasvir). Harvoni® has been approved for treatment of chronic hepatitis C. For treatment-naïve patients with genotype 1 infection without liver cirrhosis the recommended duration of treatment is 8 weeks. In this non-interventional study treatment with Harvoni® will be performed exactly according to the label.
The study drug will kindly be provided by Gilead.
- Conditions
- Chronic Hepatitis C
- Being tested
- Sofosbuvir 400mg / Ledipasvir 90 mg (FDC)
- Keywords
- CHC, IVDA (intravenous drug abuse), Hepatitis C, Sofosbuvir, Ledipasvir, Opiate Substitution Therapy
- Medical subject headings
- Hepatitis C, Chronic, Substance Abuse, Intravenous, Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sofosbuvir 400mg / Ledipasvir 90 mg (FDC)Drug
Also called Harvoni
| Study group | Role | What they receive |
|---|---|---|
| Sofosbuvir 400mg/Ledipasvir 90 mg | Other | Subjects will receive sofosbuvir 400mg q.d p.o and ledipasvir 90 mg q.d p.o (FDC) for 8 weeks Receives: Drug: Sofosbuvir 400mg / Ledipasvir 90 mg (FDC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of pills taken during the treatment phase will be calculated as a parameter for adherence to therapy for each individual subject.
Study drugs will administered daily together with the opiate substitution therapy under the supervision of qualified site personnel and recorded on a worksheet for each subject. At the end of the treatment phase, the total number of DAA pills taken will be assessed as percentage for each subject and for the whole study population.
Measured: 8 Weeks
Secondary outcomes (3)
Sustained Virologic Response (SVR) 12 Weeks after End of Therapy (SVR 12)
Viral load will be measured via PCR 12 Weeks after the End of Therapy
Measured: 12 Weeks after end of Therapy
Sustained Virologic Response (SVR) 24 Weeks after End of Therapy (SVR 24)
Viral load will be measured via PCR (polymerase chain reaction) 24 Weeks after the End of Therapy
Measured: 24 Weeks after end of Therapy
Safety and tolerability (total number of observed adverse events)
Safety and tolerability of Ledipasvir/Sofosbuvir in patients with chronic hepatitis C under opiate substitution therapy at a low threshold facility will be assessed by reporting total number of adverse event and laboratory abnormalities observed in each patient. Total number of observed adverse events and laboratory abnormalities will be reported tabulated by body system. Adverse events will be observed during the 8 weeks treatment phase and the 12 week follow up phase, for a total duration of 20 weeks.
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2015 (estimated)
- Study startSep 2015
- Primary completionSep 2016 (estimated)
- Study completionSep 2016 (estimated)
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 Chronic Hepatitis CStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wilhelminenspital Vienna
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Principal investigator, Michael Gschwantler, Wilhelminenspital Vienna
- Investigators
- Michael Gschwantler, Prof. MD, Principal investigator, Wilhelminenspital Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02638233
- Sponsor's protocol ID
- WIL4ME2015/01
- Status last verified
- Dec 2015
- First submitted
- 5 Oct 2015
- Last updated
- 23 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Schutz A, Moser S, Schwanke C, Schubert R, Luhn J, Gutic E, Lang T, Schleicher M, Haltmayer H, Gschwantler M. Directly observed therapy of chronic hepatitis C with ledipasvir/sofosbuvir in people who inject drugs at risk of nonadherence to direct-acting antivirals. J Viral Hepat. 2018 Jul;25(7):870-873. doi: 10.1111/jvh.12857. Epub 2018 Feb 6.
PubMed 29316001
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Direct Observed Therapy With Ledipasvir/Sofosbuvir in Treatment-naïve Patients With Chronic Genotype 1 HCV (Hepatitis C Virus) Infection Receiving Opiate Substitution Therapy
- ClinicalTrials.gov ID
- NCT02638233
- Acronym / sponsor ID
- WIL4ME2015/01
- Conditions
- Chronic Hepatitis C
- Keywords
- CHC, IVDA (intravenous drug abuse), Hepatitis C, Sofosbuvir, Ledipasvir, Opiate Substitution Therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Wilhelminenspital ViennaUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- Sep 2015
- Primary completion
- Sep 2016 (estimated)
- Study completion
- Sep 2016 (estimated)
- First posted
- 23 Dec 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.
Patients with chronic hepatitis C that are under opiate substitution therapy are likely to have psychiatric comorbidities such as depression; hence an Interferon based therapy is contraindicated. Additionally many of these patients have a borderline compliance, which makes it impossible to treat them at specialized hepatological centers. An ideal opportunity to treat this patients is treatment with DAAs (Direct Acting Antiviral) which can be administered daily together with the opiate substitution therapy at a low threshold facility.
Detailed description
Background:
Patients with active or previous i.v.-drug abuse and patients receiving opiate substitution therapy (OST) represent a major subgroup of the patients with chronic hepatitis C (CHC). Till some years ago it was held, that patients with a history of i.v.-drug abuse and patients receiving OST should not be considered for interferon-based antiviral treatment because of their poor compliance. However, during the past years it became clear, that patients on OST who are considered to be stable by their physicians are good candidates for antiviral therapy. Several studies have shown that SVR (sustained virological response rates) achieved in these patients are similar to results in patients without a history of i.v. drug abuse.
Subgroups of patients receiving OST:Patients receiving OST represent a very heterogeneous population. However, based on empirical observation of the behavior/compliance of each individual patient they can be assigned to one of the following three groups:
Group 1: Patients with very good compliance. These patients do not take drugs anymore and demonstrate a very good compliance. If anti HCV therapy is indicated, these patients can be referred to and treated at a hepatologic Center (i.e. hospital). Such patients have been included in various phase III trials of new direct acting antiviral agents (DAAs).
Group 2: Patients with a very poor compliance. These patients do not keep appointments (regardless whether it is at a low threshold facility or at a hospital). Due to their lack of compliance antiviral therapy of these patients is not feasible.
Group 3: Patients with a borderline compliance. These patients do come to a low threshold facility on a daily basis where they get OST under direct observation of a physician or a nurse. These patients are reluctant to go to specialized hepatitis centers (high inhibition threshold) and hence cannot be treated there. However, anti-HCV treatment can be applied together with OST under direct observation of a physician or a nurse at the low threshold facilities. The "Ambulatorium Suchthilfe Wien" a "low threshold facility" (LTF): The "Ambulatorium Suchthilfe Wien" is a facility that offers medical care to patients with active or former i.v. drug abuse (= (ex-)PWIDs). The medical team at these low-threshold facilities (=LTFs) includes general practitioners, specialists in internal medicine, psychiatrists and nurses. In contrast to hospitals (hepatologic centers in Austria with outpatient clinics in a large hospital), where there is a relatively high "psychological" inhibition threshold for PWIDs with CHC, the LTFs are located in "normal" houses. The setting is such that the "psychological" inhibition threshold for PWIDs to go there is low. At the LTFs (ex-)PWIDs can obtain OST on a daily basis under direct observation of a physician or a nurse. Hence, the patients have a high motivation to come to these facilities daily (to avoid withdrawal symptoms - they do not have a similar incentive/interest/motivation to go to a hospital on a regular basis). The direct observed OST prevents potential selling of medication on the black market. Anti-HCV treatment at the "Ambulatorium Suchthilfe Wien":
Univ.-Prof. Dr. Michael Gschwantler, an experienced hepatologist is cooperating with the "Ambulatorium Suchthilfe Wien" (=LTF). He visits the facility at least once a week (and immediately in the case of any serious problem) and takes care of the patients with regards to hepatitis/liver diseases. Prof. Gschwantler does this voluntarily and unsalaried. He performs routine laboratory and sonographic evaluation of the liver directly at the LTF. Prof. Gschwantler has already treated a small number of eligible "group 3 patients" (patients with borderline compliance as described before) with interferon-based treatment directly at the LTF (patients didn't need to go to a hospital). However, beside compliance issues contraindications against interferon (e.g. due to depression) prevent many (ex-)PWIDs from being treated at the moment.
Study drug:
In this non-interventional study patients with chronic hepatitis C, genotype 1, will be treated with Harvoni® (Sofosbuvir/Ledipasvir). Harvoni® has been approved for treatment of chronic hepatitis C. For treatment-naïve patients with genotype 1 infection without liver cirrhosis the recommended duration of treatment is 8 weeks. In this non-interventional study treatment with Harvoni® will be performed exactly according to the label.
The study drug will kindly be provided by Gilead.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sofosbuvir 400mg/Ledipasvir 90 mg | Other | Drug: Sofosbuvir 400mg / Ledipasvir 90 mg (FDC)Subjects will receive sofosbuvir 400mg q.d p.o and ledipasvir 90 mg q.d p.o (FDC) for 8 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Chronic genotype 1 HCV infection
- Fibrosis F0-F3 (i.e. non-cirrhotic confirmed by Fibroscan <12.5kPa)
- Stable opiate substitution therapy
- Regular visits at the low threshold facility during the last month
Key exclusion criteria (5 listed)
- Lack or unwillingness of safe contraception, pregnancy
- Liver cirrhosis (Fibroscan ≥12.5kPa)
- Coinfection with HBV (Hepatitis B Virus) or HIV (coinfection with HIV is excluded only because there are very few coinfected patients under care at the "Ambulatorium Suchthilfe Wien" and hence this subpopulation would be very small)
- Severe comorbidities resulting in a life expectancy of less than five years
- HCC (Hepatocellular carcinoma)
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 |
|---|---|---|
| Sofosbuvir 400mg / Ledipasvir 90 mg (FDC)Also: Harvoni | Drug | Sofosbuvir 400mg/Ledipasvir 90 mg |
Primary outcome
Percentage of pills taken during the treatment phase will be calculated as a parameter for adherence to therapy for each individual subject.
Time frame: 8 Weeks
Study drugs will administered daily together with the opiate substitution therapy under the supervision of qualified site personnel and recorded on a worksheet for each subject. At the end of the treatment phase, the total number of DAA pills taken will be assessed as percentage for each subject and for the whole study population.
3 secondary outcomes
Sustained Virologic Response (SVR) 12 Weeks after End of Therapy (SVR 12)
Time frame: 12 Weeks after end of Therapy
Sustained Virologic Response (SVR) 24 Weeks after End of Therapy (SVR 24)
Time frame: 24 Weeks after end of Therapy
Safety and tolerability (total number of observed adverse events)
Time frame: 20 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2015.
- Derived from this study: PubMed 29316001Schutz A, Moser S, Schwanke C, Schubert R, Luhn J, Gutic E, Lang T, Schleicher M, Haltmayer H, Gschwantler M. Directly observed therapy of chronic hepatitis C with ledipasvir/sofosbuvir in people who inject drugs at risk of nonadherence to direct-acting antivirals. J Viral Hepat. 2018 Jul;25(7):870-873. doi: 10.1111/jvh.12857. Epub 2018 Feb 6.
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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.
Michael Gschwantler, Prof. MD principal investigator
Wilhelminenspital Vienna
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 Sofosbuvir 400mg / Ledipasvir 90 mg (FDC) in people with Chronic Hepatitis C, run by Wilhelminenspital Vienna at 1 site in Austria.
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 5 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: status not confirmed, as of the sponsor's last update on 23 Dec 2015. 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 Austria. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michael Gschwantler, Prof. MD (0043 1 49150 2401, michael.gschwantler@wienkav.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of pills taken during the treatment phase will be calculated as a parameter for adherence to therapy for each individual subject. (time frame: 8 Weeks). 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 NCT02638233, 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 23 Dec 2015.