Chronic Hepatitis CPhase 4DARGEN-3NCT00830609
High Dose Versus Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 3
A Phase 4 study testing Peginterferon alfa 2 A, Peginterferon alfa 2 A, ribavirin + Epo Beta and ribavirin in people with Chronic Hepatitis C, run by Dr. Conrado Fernandez at 28 sites in Spain.
Trial summary
The rate of sustained virological response (SVR) in patients with chronic hepatitis C, genotype 3, high viral load and without rapid virological response (RNA-HCV negative at week 4) is low. Standard of care of these patients include treatment with weekly peginterferon plus 800 mg/day of ribavirin (RBV). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- Peginterferon alfa 2 A, Peginterferon alfa 2 A, ribavirin + Epo Beta and ribavirin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 28 sitesSpain
- Study dates
- Nov 2008to Dec 2011
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HCV Genotype 3
- RNA-HCV > > 600.000 IU/ml.
- Compromise to use contraceptive measures on treatment until 6 months after the end of treatment.
Who cannot join
- Pregnant or breastfeeding females.
- Concurrent treatment with antineoplastic or immunomodulatory agents, including corticosteroids or radiation therapy over the last 6 months before starting the trial
- Treatment with investigational drugs < 6 weeks before starting the trial
- Chronic liver disease other than hepatitis C.
- Evidence of hepatocellular carcinoma.
- Evidence of carcinoma hepatocellular
Show all 19Show fewer
- Decompensated liver disease
- Baseline Neutrophil count < 1500/cc; or Platelet count < 90,000/cc
- Baseline Hemoglobin <12 g/dL in females o <13 g/dL in males.
- Increased risk of anemia(Eg, thalassemia, spherocytosis..).
- Ischemic heart disease or cerebrovascular disease.
- Serum creatinine >1.5 times upper limit of normality.
- History of severe psychiatric conditions (Major antidepressives or neuroleptic drugs required for major depression or psychosis), suicide attempts or psychiatric disability .
- History of convulsive disorders.
- Immunological conditions.
- Chronic Obstructive Lung Disease with limited functionality
- Severe heart disease or congestive cardiac insufficiency cardiopathy grave.
- Advanced atherosclerosis
- Solid organ or bone marrow transplant.
Trial locations and contacts
28 sites in 1 country.
28 sites in 1 country
Spain28 sites
Hospital Fundación Alcorcón
Alcorcón, Madrid, 28922
Hospital Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital del Mar
Barcelona, Barcelona, 08003
Hospital Clinic i Provincial de Barcelona
Barcelona, Barcelona, 08036
Hospital Universitario Reina Sofía
Córdoba, Córdoba, 14004
Hospital de Donostia
Donostia / San Sebastian, Guipuzcoa, 20014
Hospital de Getafe
Getafe, Madrid, 28901
Hospital Universitario Virgen de las Nieves
Granada, Granada, 18004
Hospital San Cecilio
Granada, Granada
Hospital de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
Hospital de León
León, León, 24071
Hospital La Princesa
Madrid, Madrid, 28006
Hospital Gregorio Marañon
Madrid, Madrid, 28007
Hospital 12 de Octubre
Madrid, Madrid, 28021
Hospital Ramón y Cajal
Madrid, Madrid, 28034
Hospital Puerta de Hierro
Majadahonda, Madrid, 28222
Hospital Clínico Universitario Virgen de la Victoria
Málaga, Málaga, 29010
Hospital Costa del Sol
Marbella, Málaga, 29603
Hospital Central de Asturias
Oviedo, Oviedo, 33006
Hospital Parc Taulí
Sabadell, Barcelona, 08208
Hospital Clinico Universitario de Salamanca
Salamanca, Salamanca, 37007
Hospital Marqués de Valdecilla
Santander, Cantabria, 39008
Hospital de Valme
Seville, Sevilla, 41014
Hospital Clínico Universitario de Valencia
Valencia, Valencia, 46010
Hospital Clínico Universitario de Valladolid
Valladolid, Valladolid, 47005
Hospital Santiago Apóstol
Vitoria-Gasteiz, Vitoria, 01004
Hospital Clínico de Zaragoza
Zaragoza, Zaragoza, 50009
Hospital Miguel Servet
Zaragoza, Zaragoza, 50009
About this study
Official title: Effect of High Dose vs. Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 3, High Viral Load Without Rapid Virological Response
The rate of sustained virological response (SVR) in patients with chronic hepatitis C, genotype 3, high viral load and without rapid virological response (RNA-HCV negative at week 4) is low. Standard of care of these patients include treatment with weekly peginterferon plus 800 mg/day of ribavirin (RBV). Extended treatment to 48 weeks does not provide more clinical benefit than the standard duration. The main hypothesis is that higher dose of ribavirin may be better in terms of SVR than the standard dose.
Read the detailed description
Aims:
- Efficacy 1.1) Rate of RNA-HCV negative at week 4 and 24 in each arm. 1.2) Rate of SVR in each arm.
- Safety 2.1) Rate of adverse effects in each arm.
Design: Randomized controlled trial.
Patients will be randomly allocated into three arms:
Arm A : Peginterferon α-2a (180 μg/week)SC. plus Ribavirin (800 mg/day) p.o. over 24 weeks.
Arm B: Peginterferon α-2a (180 μg/week) plus Ribavirin (1600 mg/day) with support of Epoetin β (450 IU/kg/week) SC over 4 weeks:
B1.- If RNA-HCV undetectable at week 4, standard of care will be continued (Peginterferon α-2a, 180 μg/wee plus Ribavirin (800 mg/day) over 20 additional weeks).
B2.- If RNA-HCV were detectable at week 4, treatment will be continued with peginterferon α-2a (180 μg/week) plus RBV(1,600 mg/day) plus Epoetin β (450 UI/kg/week) over 20 additional weeks.
Sample size: 111 patients. To increase the SVR from 50% to 75%. Beta: 0.1; alfa: 0.05; Loss: 15%.
Randomization will be 1:2, 37 patients in Group A and 74 patients in group B.
- Conditions
- Chronic Hepatitis C
- Being tested
- Peginterferon alfa 2 A, Peginterferon alfa 2 A, ribavirin + Epo Beta, ribavirin, Peginterferon alfa 2
- Keywords
- Chronic Hepatitis C, Genotype 3, High viral load
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Peginterferon alfa 2 ADrug
Also called Pegasys
Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 800 mg/day po (Control Group) Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day po plus Epoetin β (450 IU/kg/week) SC over 4 weeks (Arm B1) Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day po plus Epo beta 450 UI over four weeks (Arm B1) If RNA-HCV positive at week 4, Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day plus Epo beta 450 UI to keep Hb>12 g/dL if required over 20 additional weeks (Arm B2)
Peginterferon alfa 2 A, ribavirin + Epo BetaDrug
Also called Pegasys
Ribavirin 1,600 mg/day plus peginterferon alfa 2A 180 mcg/week plus Epo beta 450 IU/Kg/day to maintain Hb>12g/dl over 4 or 24 weeks
ribavirinDrug
Also called peginterferon alfa 2 a, Epoetin beta
RBV 1600 mg/day 24 weeks
ribavirinDrug
Also called Pegasys
ribavirin 800 mg/day for 24 weeks
Peginterferon alfa 2Drug
Also called Pegasys
Peginterferon alfa 2 a 180 mcg/week for 4 weeks and then peginterferon alfa 2A for 20 weeks
ribavirinDrug
Also called Pegasys
RBV 1600 mg/day 4 weeks and then ribavirin 800 mg/day 20 weeks
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Patients in this arm will receive standard of care (Peginterferon alfa 2A 180 mcg/weeks SC plus ribavirin 800 mg/day for 24 weeks). Receives: Drug: Peginterferon alfa 2 A; Drug: ribavirin |
| B1 | Experimental | After a period of 4 weeks with peginterferon alfa 2 a 180 mcg/week plus RBV 1600 mg/day (Induction phase), these patients will be allocated according to negativity or positivity of RNA-HCV at week 4. If RNA-HCV negative, treatment with peginterferon alfa 2 a 180 mcg/week plus RBV 800 mg/day (SOC) will be continued over 20 additional weeks (Arm B1). Epo β (450 IU/kg/week) will be administered as required to maintain hemoglobin > 12g/dL. Receives: Drug: Peginterferon alfa 2 A; Drug: Peginterferon alfa 2 A, ribavirin + Epo Beta; Drug: Peginterferon alfa 2; Drug: ribavirin |
| B2 | Experimental | If RNA-HCV at week 4 remains positive after the induction phase, then peginterferon alfa 2 a 180 mcg/week plus RBV 1600 mg/day will be continued for 20 additional weeks (Arm B2). Epo β (450 IU/kg/week) will be administered as required to maintain hemoglobin > 12g/dL. Receives: Drug: Peginterferon alfa 2 A; Drug: Peginterferon alfa 2 A, ribavirin + Epo Beta; Drug: ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of patients with RNA-HCV negative in each arm at week 24 after the end of treatment.
Measured: 1 year
Secondary outcomes (1)
Rate of patients with undetectable RNA-HCV in each arm at week 4 and 24 of treatment. Rate of adverse effects in each arm.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2009 (estimated)
- Study startNov 2008
- Primary completionSep 2011
- Study completionDec 2011
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Conrado Fernandez
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. Conrado Fernandez, Hospital Universitario Fundación Alcorcón
- Investigators
- Conrado M Fernandez-Rodriguez, Study director, Hospital Universitario Fundacion Alcorcon; University Rey Juan Carlos.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00830609
- Sponsor's protocol ID
- ROCHE FARMA S.A.
- Acronym
- DARGEN-3
- Status last verified
- Mar 2012
- First submitted
- 27 Jan 2009
- Last updated
- 13 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fernandez-Rodriguez CM, Morillas RM, Masnou H, Navarro JM, Barcena R, Gonzalez JM, Martin-Martin L, Poyato A, Miquel-Planas M, Jorquera F, Casanovas T, Salmeron J, Calleja JL, Sola R, Alonso S, Planas R, Romero-Gomez M. Randomized clinical trial comparing high versus standard dose of ribavirin plus peginterferon alfa-2a in hepatitis C genotype 3 and high viral load. Dargen-3 study. Gastroenterol Hepatol. 2014 Jan;37(1):1-8. doi: 10.1016/j.gastrohep.2013.10.005. Epub 2013 Dec 17.
PubMed 24360571
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of High Dose vs. Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 3, High Viral Load Without Rapid Virological Response
- ClinicalTrials.gov ID
- NCT00830609
- Acronym / sponsor ID
- DARGEN-3 / ROCHE FARMA S.A.
- Conditions
- Chronic Hepatitis C
- Keywords
- Chronic Hepatitis C, Genotype 3, High viral load
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Dr. Conrado FernandezUniversity, hospital or other
- Study start
- Nov 2008
- Primary completion
- Sep 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 28 Jan 2009 (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 rate of sustained virological response (SVR) in patients with chronic hepatitis C, genotype 3, high viral load and without rapid virological response (RNA-HCV negative at week 4) is low. Standard of care of these patients include treatment with weekly peginterferon plus 800 mg/day of ribavirin (RBV). Extended treatment to 48 weeks does not provide more clinical benefit than the standard duration. The main hypothesis is that higher dose of ribavirin may be better in terms of SVR than the standard dose.
Detailed description
Aims:
- Efficacy 1.1) Rate of RNA-HCV negative at week 4 and 24 in each arm. 1.2) Rate of SVR in each arm.
- Safety 2.1) Rate of adverse effects in each arm.
Design: Randomized controlled trial.
Patients will be randomly allocated into three arms:
Arm A : Peginterferon α-2a (180 μg/week)SC. plus Ribavirin (800 mg/day) p.o. over 24 weeks.
Arm B: Peginterferon α-2a (180 μg/week) plus Ribavirin (1600 mg/day) with support of Epoetin β (450 IU/kg/week) SC over 4 weeks:
B1.- If RNA-HCV undetectable at week 4, standard of care will be continued (Peginterferon α-2a, 180 μg/wee plus Ribavirin (800 mg/day) over 20 additional weeks).
B2.- If RNA-HCV were detectable at week 4, treatment will be continued with peginterferon α-2a (180 μg/week) plus RBV(1,600 mg/day) plus Epoetin β (450 UI/kg/week) over 20 additional weeks.
Sample size: 111 patients. To increase the SVR from 50% to 75%. Beta: 0.1; alfa: 0.05; Loss: 15%.
Randomization will be 1:2, 37 patients in Group A and 74 patients in group B.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: Peginterferon alfa 2 A, Drug: ribavirinPatients in this arm will receive standard of care (Peginterferon alfa 2A 180 mcg/weeks SC plus ribavirin 800 mg/day for 24 weeks). |
| B1 | Experimental | Drug: Peginterferon alfa 2 A, Drug: Peginterferon alfa 2 A, ribavirin + Epo Beta, Drug: Peginterferon alfa 2, Drug: ribavirinAfter a period of 4 weeks with peginterferon alfa 2 a 180 mcg/week plus RBV 1600 mg/day (Induction phase), these patients will be allocated according to negativity or positivity of RNA-HCV at week 4. If RNA-HCV negative, treatment with peginterferon alfa 2 a 180 mcg/week plus RBV 800 mg/day (SOC) will be continued over 20 additional weeks (Arm B1). Epo β (450 IU/kg/week) will be administered as required to maintain hemoglobin > 12g/dL. |
| B2 | Experimental | Drug: Peginterferon alfa 2 A, Drug: Peginterferon alfa 2 A, ribavirin + Epo Beta, Drug: ribavirinIf RNA-HCV at week 4 remains positive after the induction phase, then peginterferon alfa 2 a 180 mcg/week plus RBV 1600 mg/day will be continued for 20 additional weeks (Arm B2). Epo β (450 IU/kg/week) will be administered as required to maintain hemoglobin > 12g/dL. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- HCV Genotype 3
- RNA-HCV > > 600.000 IU/ml.
- Compromise to use contraceptive measures on treatment until 6 months after the end of treatment.
Key exclusion criteria (19 listed)
- Pregnant or breastfeeding females.
- Concurrent treatment with antineoplastic or immunomodulatory agents, including corticosteroids or radiation therapy over the last 6 months before starting the trial
- Treatment with investigational drugs < 6 weeks before starting the trial
- Chronic liver disease other than hepatitis C.
- Evidence of 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 |
|---|---|---|
| Peginterferon alfa 2 AAlso: PegasysPeginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 800 mg/day po (Control Group) Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day po plus Epoetin β (450 IU/kg/week) SC over 4 weeks (Arm B1) Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day po plus Epo beta 450 UI over four weeks (Arm B1) If RNA-HCV positive at week 4, Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day plus Epo beta 450 UI to keep Hb>12 g/dL if required over 20 additional weeks (Arm B2) | Drug | A, B1, B2 |
| Peginterferon alfa 2 A, ribavirin + Epo BetaAlso: PegasysRibavirin 1,600 mg/day plus peginterferon alfa 2A 180 mcg/week plus Epo beta 450 IU/Kg/day to maintain Hb>12g/dl over 4 or 24 weeks | Drug | B1, B2 |
| ribavirinAlso: peginterferon alfa 2 a, Epoetin betaRBV 1600 mg/day 24 weeks | Drug | B2 |
| ribavirinAlso: Pegasysribavirin 800 mg/day for 24 weeks | Drug | A |
| Peginterferon alfa 2Also: PegasysPeginterferon alfa 2 a 180 mcg/week for 4 weeks and then peginterferon alfa 2A for 20 weeks | Drug | B1 |
| ribavirinAlso: PegasysRBV 1600 mg/day 4 weeks and then ribavirin 800 mg/day 20 weeks | Drug | B1 |
Primary outcome
Rate of patients with RNA-HCV negative in each arm at week 24 after the end of treatment.
Time frame: 1 year
1 secondary outcome
Rate of patients with undetectable RNA-HCV in each arm at week 4 and 24 of treatment. Rate of adverse effects in each arm.
Time frame: 1 year
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 13 Mar 2012.
- Derived from this study: PubMed 24360571Fernandez-Rodriguez CM, Morillas RM, Masnou H, Navarro JM, Barcena R, Gonzalez JM, Martin-Martin L, Poyato A, Miquel-Planas M, Jorquera F, Casanovas T, Salmeron J, Calleja JL, Sola R, Alonso S, Planas R, Romero-Gomez M. Randomized clinical trial comparing high versus standard dose of ribavirin plus peginterferon alfa-2a in hepatitis C genotype 3 and high viral load. Dargen-3 study. Gastroenterol Hepatol. 2014 Jan;37(1):1-8. doi: 10.1016/j.gastrohep.2013.10.005. Epub 2013 Dec 17.
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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.
Conrado M Fernandez-Rodriguez study director
Hospital Universitario Fundacion Alcorcon; University Rey Juan Carlos.
28 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Peginterferon alfa 2 A, Peginterferon alfa 2 A, ribavirin + Epo Beta and ribavirin in people with Chronic Hepatitis C, run by Dr. Conrado Fernandez at 28 sites in Spain.
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 3 inclusion and 19 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 13 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in Spain. 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 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?
Rate of patients with RNA-HCV negative in each arm at week 24 after the end of treatment. (time frame: 1 year). 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 NCT00830609, 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 13 Mar 2012.