NCT01231685

Brief 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. 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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
9

participants targeted

Target at below P25 for phase_2 hiv

Timeline
Completed

Started Dec 2011

Longer than P75 for phase_2 hiv

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 29, 2010

Completed
3 days until next milestone

First Posted

Study publicly available on registry

November 1, 2010

Completed
1.1 years until next milestone

Study Start

First participant enrolled

December 1, 2011

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2016

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2016

Completed
Last Updated

September 21, 2016

Status Verified

September 1, 2016

Enrollment Period

4.3 years

First QC Date

October 29, 2010

Last Update Submit

September 20, 2016

Conditions

HIVHepatitis CLiver Fibrosis

Keywords

Liver fibrosisHIVHepatitis C VirusCoinfection

Outcome Measures

Primary Outcomes (1)

  • To evaluate the effect of switch on change in liver fibrosis score

    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

    48 weeks

Secondary Outcomes (4)

  • To evaluate inflammatory markers associated with liver fibrosis

    72 weeks

  • To evaluate effect of switch on hepatic function

    72 weeks

  • To evaluate effect of switch on metabolic parameters

    72 weeks

  • Immunologic and virologic safety

    72 weeks

Study Arms (2)

ritonavir-boosted protease inhibitor

ACTIVE COMPARATOR
Drug: RaltegravirDrug: Ritonavir-boosted protease inhibitor

Raltegravir

EXPERIMENTAL
Drug: RaltegravirDrug: Ritonavir-boosted protease inhibitor

Interventions

RaltegravirDRUG

Subjects will maintain their nucleoside backbone and switch ritonavir-boosted protease inhibitor to Raltegravir 400 mg po BID for 48 weeks.

Also known as: Isentress, MK-0518, RGV
Raltegravirritonavir-boosted protease inhibitor
Ritonavir-boosted protease inhibitorDRUG

Subjects will maintain their nucleoside backbone and remain on a ritonavir-boosted protease inhibitor at standard doses for for 48 weeks

Also known as: Kaletra, Lopinavir-ritonavir, Atazanavir-ritonavir, Reyataz-norvir, Darunavir-ritonavir, Presista-norvir
Raltegravirritonavir-boosted protease inhibitor

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).
  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Providence Health Care- St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

University Health Network - Toronto General Hospital Division

Toronto, Ontario, M5G2N2, Canada

Location

Montreal Chest Institute

Montreal, Quebec, Canada

Location

Related Publications (2)

  • 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.

    PMID: 20032006BACKGROUND

  • Eron 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.

    PMID: 20074791BACKGROUND

MeSH Terms

Conditions

Hepatitis CLiver CirrhosisCoinfection

Interventions

Raltegravir Potassiumlopinavir-ritonavir drug combinationLopinaviratazanavir, ritonavir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System DiseasesFibrosisPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PyrrolidinonesPyrrolidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPyrimidinonesPyrimidines

Study Officials

  • Marina B Klein, MD. M.Sc.

    McGill University Health Centre/Research Institute of the McGill University Health Centre

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

October 29, 2010

First Posted

November 1, 2010

Study Start

December 1, 2011

Primary Completion

March 1, 2016

Study Completion

September 1, 2016

Last Updated

September 21, 2016

Record last verified: 2016-09

Locations

CA(3)