HIVPhase 2NCT01231685
Raltegravir Switch Study to Reduce Liver Fibrosis Progression in HIV-Hepatitis C Co-infection
A Phase 2 study testing Raltegravir and Ritonavir-boosted protease inhibitor in people with HIV and Hepatitis C, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 3 sites in Canada.
Trial summary
HIV infection exerts a negative impact on the course of HCV infection. Co-infected individuals progress more rapidly to liver fibrosis, cirrhosis and ESLD compared to those infected with HCV alone. Some of the this accelerated fibrosis may be related to longterm chronic toxicity from protease inhibitor based ART. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV, Hepatitis C, Liver Fibrosis
- What is being tested?
- Raltegravir and Ritonavir-boosted protease inhibitor
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 3 sitesCanada
- Study dates
- Dec 2011to Sep 2016
- Phase
- Phase 2
- 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
- 18 years or older
- Chronic HIV-HCV co-infection (HCV RNA + for at least 6 months and could have had previous HCV treatment).
- Receiving ritonavir boosted PI-based ART for at least 6 months.
- APRI score ≥ 1.5 (equivalent to liver biopsy score of ≥ F2) AND/OR Fibroscan > 6.9KPa
- HIV viral suppression (<50 copies/mL) for at least 6 months.
- No prior evidence of resistance to raltegravir or co-administered nucleoside backbone.
- No prior history of virologic failure.
Who cannot join
- Clinical evidence of decompensated liver disease (e.g., ascites, esophageal varices, or hepatic encephalopathy hepatoma or hepatocellular carcinoma).
- Chronic Hepatitis B infection (defined as positive HBsAg or Hepatitis B viral load greater than 10,000 copies/mL).
- AFP greater than or equal to 200 ng/mL at screening.
- Known or suspected Wilson's disease, alpha-1-antitrypsin deficiency, celiac disease or other cause of chronic liver disease.
- Chronic renal insufficiency (eGFR < 20 mL/min) at screening.
- Pregnancy and planned pregnancy (WOCBP not using adequate contraception).
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- Women who are breastfeeding.
- Active opportunistic infection (except oral thrush) or neoplasm (except Kaposi's sarcoma, skin cancer, or cancer of the cervix or anus, unless known or suspected liver metastasis).
- Patients intending to start HCV therapy within the treatment phase (within the year following the baseline visit).
Trial locations and contacts
3 sites in 1 country.
Canada3 sites
Montreal Chest Institute
Montreal, Quebec
University Health Network - Toronto General Hospital Division
Toronto, Ontario, M5G2N2
Providence Health Care- St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
About this study
Official title: A Randomized Prospective Open Label Study of Switching to Raltegravir Based ART Compared to Maintaining Ritonavir Boosted PI-based ART on Liver Fibrosis Progression in HIV-HCV Coinfected Patients
HIV infection exerts a negative impact on the course of HCV infection. Co-infected individuals progress more rapidly to liver fibrosis, cirrhosis and ESLD compared to those infected with HCV alone. Some of the this accelerated fibrosis may be related to longterm chronic toxicity from protease inhibitor based ART.
Hypothesis: Switching from ritonavir boosted-PI based ART regimen to a Raltegravir-based regimen will reduce the rate of hepatic fibrosis progression in HIV-HCV co-infected patients as measured by transient elastography (Fibroscan®) and the AST-to-platelet ratio index (APRI).
Read the detailed description
Primary Objective-To assess if switching from ritonavir boosted-PI based ART regimen to a Raltegravir-based regimen will reduce the rate of hepatic fibrosis progression in HIV-HCV co-infected patients as measured by transient elastography (Fibroscan®) and the AST-to-platelet ratio index (APRI) after 48 weeks of treatment.
Secondary Objectives:
(i) To assess the safety and tolerability of switching from a ritonavir boosted-PI ART regimen to a raltegravir-based regimen for 48 weeks.
(ii) To evaluate hepatic function (liver enzymes) at weeks 0, 2, 4, 8, 12, 24, 36, 48 and 72 post switch.
(iii) To evaluate the effect of switching treatment on control of HIV infection (as measured by HIV viral load and CD4) at weeks 0, 4, 8, 12, 24, 36, 48, and 72 post switch.
(iv) To evaluate metabolic profiles (e.g, fasting lipid profiles, glucose and insulin) at weeks 0, 24, 48 and 72 post switch.
(v) To evaluate inflammatory markers associated with liver fibrosis at weeks 0, 2, 4, 8, 12, 24, 36, 48 and 72 post switch.
Population: Patients will be selected from CTN222; a Canadian National multisite prospective cohort of HCV-HIV infected persons (N=978) or from other eligible patients followed at participating sites. All patients recruited into the cohort are adults aged over 16 years old with documented HIV infection (ELISA with western blot confirmation) and with chronic HCV infection or evidence of HCV exposure (e.g. HCV-seropositive by ELISA with RIBA II or EIA confirmation, or if serologically false negative, HCV RNA+).
Study Design: A Randomized Prospective Open label study
Sample Size:
N = 40 This is a Phase II study designed to evaluate the safety and feasibility of a switch to raltegravir in HIV-HCV co-infected patients. As neither the duration of time required to improve fibrosis nor the potential impact of such a switch currently is known, this trial will provide important pilot data with which to estimate the true effect size and calculate the sample size required to conduct a larger definitive study on this question. It is hypothesized that switching therapy will lead to significant reduction in fibrosis as measured by APRI and FibroScan®. In other studies, for example, of successful HCV treatment using FibroScan®, a 34% reduction in fibrosis score was observed in those obtaining a sustained virologic response at 48 weeks (e.g., from mean baseline score of 10.3 kPa to 6.6 kPa at 48 weeks; s.d.= 5 kPa 1). We propose a sample size of 20 patients in each group, which would provide approximately 80% power to detect at least a difference of 5 kPa in fibrosis score change between the two groups assuming a similar standard deviation.
- Conditions
- HIV, Hepatitis C, Liver Fibrosis
- Being tested
- Raltegravir, Ritonavir-boosted protease inhibitor
- Keywords
- Liver fibrosis, HIV, Hepatitis C Virus, Coinfection
- Medical subject headings
- Hepatitis C, Liver Cirrhosis, Coinfection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RaltegravirDrug
Also called Isentress, MK-0518, RGV
Subjects will maintain their nucleoside backbone and switch ritonavir-boosted protease inhibitor to Raltegravir 400 mg po BID for 48 weeks.
Ritonavir-boosted protease inhibitorDrug
Also called Kaletra, Lopinavir-ritonavir, Atazanavir-ritonavir, Reyataz-norvir
Subjects will maintain their nucleoside backbone and remain on a ritonavir-boosted protease inhibitor at standard doses for for 48 weeks
| Study group | Role | What they receive |
|---|---|---|
| ritonavir-boosted protease inhibitor | Active comparator | Not described Receives: Drug: Raltegravir; Drug: Ritonavir-boosted protease inhibitor |
| Raltegravir | Experimental | Not described Receives: Drug: Raltegravir; Drug: Ritonavir-boosted protease inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the effect of switch on change in liver fibrosis score
Change in fibrosis will be assessed by:
- Change in Fibroscan® score (kPa) at 48 weeks from baseline
- Change in log transformed AST-to-platelt ratio (APRI) score at 48 weeks from baseline
Measured: 48 weeks
Secondary outcomes (4)
To evaluate inflammatory markers associated with liver fibrosis
As a switch from protease inhibitors based regimen to a raltegravir based regimen may impact the liver through various potential mechanisms, we will explore the impact of treatment switching on inflammatory biomarkers.
Measured: 72 weeks
To evaluate effect of switch on hepatic function
Liver enzymes, albumin, direct bilirubin and INR will be measured at week 0,2,4,8,12,24,36,40 and 72.
Measured: 72 weeks
To evaluate effect of switch on metabolic parameters
Metabolic parameters, such as fasting glucose, lipid and insulin profiles will be measured at week 0,24 and 48 post switch
Measured: 72 weeks
Immunologic and virologic safety
To ensure safety, with respect to control of HIV infection following a switch to raltegravir, HIV viral load and CD4 cell counts will be measured at weeks 0,4,8 12, 24, 36, 48 and 72 post switch.
Measured: 72 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2010 (estimated)
- Study startDec 2011
- Primary completionMar 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by McGill University Health Centre/Research Institute of the McGill University Health CentreThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, CIHR Canadian HIV Trials Network
- Responsible party
- Principal investigator, Marina Klein, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Investigators
- Marina B Klein, MD. M.Sc., Principal investigator, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01231685
- Sponsor's protocol ID
- CTN260
- Status last verified
- Sep 2016
- First submitted
- 29 Oct 2010
- Last updated
- 21 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Vispo E, Mena A, Maida I, Blanco F, Cordoba M, Labarga P, Rodriguez-Novoa S, Alvarez E, Jimenez-Nacher I, Soriano V. Hepatic safety profile of raltegravir in HIV-infected patients with chronic hepatitis C. J Antimicrob Chemother. 2010 Mar;65(3):543-7. doi: 10.1093/jac/dkp446. Epub 2009 Dec 23.
PubMed 20032006Eron JJ, Young B, Cooper DA, Youle M, Dejesus E, Andrade-Villanueva J, Workman C, Zajdenverg R, Fatkenheuer G, Berger DS, Kumar PN, Rodgers AJ, Shaughnessy MA, Walker ML, Barnard RJ, Miller MD, Dinubile MJ, Nguyen BY, Leavitt R, Xu X, Sklar P; SWITCHMRK 1 and 2 investigators. Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials. Lancet. 2010 Jan 30;375(9712):396-407. doi: 10.1016/S0140-6736(09)62041-9. Epub 2010 Jan 12.
PubMed 20074791
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Prospective Open Label Study of Switching to Raltegravir Based ART Compared to Maintaining Ritonavir Boosted PI-based ART on Liver Fibrosis Progression in HIV-HCV Coinfected Patients
- ClinicalTrials.gov ID
- NCT01231685
- Acronym / sponsor ID
- CTN260
- Conditions
- HIV, Hepatitis C, Liver Fibrosis
- Keywords
- Liver fibrosis, HIV, Hepatitis C Virus, Coinfection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health CentreUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, CIHR Canadian HIV Trials Network
- Study start
- Dec 2011
- Primary completion
- Mar 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 1 Nov 2010 (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.
HIV infection exerts a negative impact on the course of HCV infection. Co-infected individuals progress more rapidly to liver fibrosis, cirrhosis and ESLD compared to those infected with HCV alone. Some of the this accelerated fibrosis may be related to longterm chronic toxicity from protease inhibitor based ART.
Hypothesis: Switching from ritonavir boosted-PI based ART regimen to a Raltegravir-based regimen will reduce the rate of hepatic fibrosis progression in HIV-HCV co-infected patients as measured by transient elastography (Fibroscan®) and the AST-to-platelet ratio index (APRI).
Detailed description
Primary Objective-To assess if switching from ritonavir boosted-PI based ART regimen to a Raltegravir-based regimen will reduce the rate of hepatic fibrosis progression in HIV-HCV co-infected patients as measured by transient elastography (Fibroscan®) and the AST-to-platelet ratio index (APRI) after 48 weeks of treatment.
Secondary Objectives:
(i) To assess the safety and tolerability of switching from a ritonavir boosted-PI ART regimen to a raltegravir-based regimen for 48 weeks.
(ii) To evaluate hepatic function (liver enzymes) at weeks 0, 2, 4, 8, 12, 24, 36, 48 and 72 post switch.
(iii) To evaluate the effect of switching treatment on control of HIV infection (as measured by HIV viral load and CD4) at weeks 0, 4, 8, 12, 24, 36, 48, and 72 post switch.
(iv) To evaluate metabolic profiles (e.g, fasting lipid profiles, glucose and insulin) at weeks 0, 24, 48 and 72 post switch.
(v) To evaluate inflammatory markers associated with liver fibrosis at weeks 0, 2, 4, 8, 12, 24, 36, 48 and 72 post switch.
Population: Patients will be selected from CTN222; a Canadian National multisite prospective cohort of HCV-HIV infected persons (N=978) or from other eligible patients followed at participating sites. All patients recruited into the cohort are adults aged over 16 years old with documented HIV infection (ELISA with western blot confirmation) and with chronic HCV infection or evidence of HCV exposure (e.g. HCV-seropositive by ELISA with RIBA II or EIA confirmation, or if serologically false negative, HCV RNA+).
Study Design: A Randomized Prospective Open label study
Sample Size:
N = 40 This is a Phase II study designed to evaluate the safety and feasibility of a switch to raltegravir in HIV-HCV co-infected patients. As neither the duration of time required to improve fibrosis nor the potential impact of such a switch currently is known, this trial will provide important pilot data with which to estimate the true effect size and calculate the sample size required to conduct a larger definitive study on this question. It is hypothesized that switching therapy will lead to significant reduction in fibrosis as measured by APRI and FibroScan®. In other studies, for example, of successful HCV treatment using FibroScan®, a 34% reduction in fibrosis score was observed in those obtaining a sustained virologic response at 48 weeks (e.g., from mean baseline score of 10.3 kPa to 6.6 kPa at 48 weeks; s.d.= 5 kPa 1). We propose a sample size of 20 patients in each group, which would provide approximately 80% power to detect at least a difference of 5 kPa in fibrosis score change between the two groups assuming a similar standard deviation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ritonavir-boosted protease inhibitor | Active comparator | Drug: Raltegravir, Drug: Ritonavir-boosted protease inhibitor |
| Raltegravir | Experimental | Drug: Raltegravir, Drug: Ritonavir-boosted protease inhibitor |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 18 years or older
- Chronic HIV-HCV co-infection (HCV RNA + for at least 6 months and could have had previous HCV treatment).
- Receiving ritonavir boosted PI-based ART for at least 6 months.
- APRI score ≥ 1.5 (equivalent to liver biopsy score of ≥ F2) AND/OR Fibroscan > 6.9KPa
- HIV viral suppression (<50 copies/mL) for at least 6 months.
Key exclusion criteria (9 listed)
- Clinical evidence of decompensated liver disease (e.g., ascites, esophageal varices, or hepatic encephalopathy hepatoma or hepatocellular carcinoma).
- Chronic Hepatitis B infection (defined as positive HBsAg or Hepatitis B viral load greater than 10,000 copies/mL).
- AFP greater than or equal to 200 ng/mL at screening.
- Known or suspected Wilson's disease, alpha-1-antitrypsin deficiency, celiac disease or other cause of chronic liver disease.
- Chronic renal insufficiency (eGFR < 20 mL/min) at screening.
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 |
|---|---|---|
| RaltegravirAlso: Isentress, MK-0518, RGVSubjects will maintain their nucleoside backbone and switch ritonavir-boosted protease inhibitor to Raltegravir 400 mg po BID for 48 weeks. | Drug | Raltegravir, ritonavir-boosted protease inhibitor |
| Ritonavir-boosted protease inhibitorAlso: Kaletra, Lopinavir-ritonavir, Atazanavir-ritonavir, Reyataz-norvirSubjects will maintain their nucleoside backbone and remain on a ritonavir-boosted protease inhibitor at standard doses for for 48 weeks | Drug | Raltegravir, ritonavir-boosted protease inhibitor |
Primary outcome
To evaluate the effect of switch on change in liver fibrosis score
Time frame: 48 weeks
Change in fibrosis will be assessed by: 1. Change in Fibroscan® score (kPa) at 48 weeks from baseline 2. Change in log transformed AST-to-platelt ratio (APRI) score at 48 weeks from baseline
4 secondary outcomes
To evaluate inflammatory markers associated with liver fibrosis
Time frame: 72 weeks
To evaluate effect of switch on hepatic function
Time frame: 72 weeks
To evaluate effect of switch on metabolic parameters
Time frame: 72 weeks
Immunologic and virologic safety
Time frame: 72 weeks
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 21 Sep 2016.
- Background: PubMed 20032006Vispo E, Mena A, Maida I, Blanco F, Cordoba M, Labarga P, Rodriguez-Novoa S, Alvarez E, Jimenez-Nacher I, Soriano V. Hepatic safety profile of raltegravir in HIV-infected patients with chronic hepatitis C. J Antimicrob Chemother. 2010 Mar;65(3):543-7. doi: 10.1093/jac/dkp446. Epub 2009 Dec 23.
- Background: PubMed 20074791Eron JJ, Young B, Cooper DA, Youle M, Dejesus E, Andrade-Villanueva J, Workman C, Zajdenverg R, Fatkenheuer G, Berger DS, Kumar PN, Rodgers AJ, Shaughnessy MA, Walker ML, Barnard RJ, Miller MD, Dinubile MJ, Nguyen BY, Leavitt R, Xu X, Sklar P; SWITCHMRK 1 and 2 investigators. Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials. Lancet. 2010 Jan 30;375(9712):396-407. doi: 10.1016/S0140-6736(09)62041-9. Epub 2010 Jan 12.
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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.
Marina B Klein, MD. M.Sc. principal investigator
McGill University Health Centre/Research Institute of the McGill University Health Centre
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Raltegravir and Ritonavir-boosted protease inhibitor in people with HIV and Hepatitis C, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 3 sites in Canada.
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 7 inclusion and 9 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 21 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
To evaluate the effect of switch on change in liver fibrosis score (time frame: 48 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 NCT01231685, which also lists 2 linked publications.
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 21 Sep 2016.