SMASH: The St. Marys and The Mater Switch Study

Sponsor

Imperial College London (Other)

Overall Status

Terminated

CT.gov ID

NCT00981773

Collaborator

Mater Misericordiae University Hospital (Other)

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of the study is to determine whether switching from an antiretroviral regimen containing abacavir and/or didanosine to one containing maraviroc will lead to a reduction in platelet reactivity and inflammatory markers at weeks 12 and 24 thereby conferring a reduction in cardiac risk.

In addition the study will assess the efficacy of a maraviroc containing regimen in combination with a boosted protease inhibitor in terms of tolerability and achieving long term viral suppression as assessed at week 48.

The investigators hypothesize that there will be a rapid reduction in platelet reactivity on switching to maraviroc and that a boosted protease inhibitor in combination with maraviroc will provide a safe and efficacious antiretroviral regimen enabling a reduction in cardiac risk whilst maintaining virological suppression.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Maraviroc Drug: Maraviroc	Phase 4

Detailed Description

To assess the safety, changes in platelet reactivity, plasma cardiac biomarkers and metabolic parameters in HIV 1 infected subjects undergoing a switch in ART from a nucleoside containing regimen which includes abacavir and / or didanosine to a maraviroc containing regimen.

40 HIV-1 infected subjects currently receiving stable antiretroviral therapy consisting of a boosted protease inhibitor and two NRTIs including abacavir and / or didanosine will be recruited. Subjects will be randomized on a 1:1 basis to one of two arms:

Arm 1 (immediate switch in antiretroviral therapy)

Continue current boosted protease inhibitor
Switch NRTI backbone to maraviroc 150 mg bid

Arm 2 (continue current antiretroviral therapy)

No change to current antiretroviral therapy for twelve weeks
After twelve weeks switch therapy as per Arm 1

Subjects will be followed up for 48 weeks and will attend for clinic visits at screening, baseline, weeks 4, 12, 16, 24, 36 and 48. Platelet reactivity, inflammatory and cardiac biomarkers and markers of T cell activation will be assessed at baseline, week 12 and week 24.

Following completion of the study subjects may continue their study antiretroviral regimen or switch to an alternative regimen at their clinician's discretion.

Inclusion Criteria

HIV-1 infected males or females
Between 18 and 65 years of age
Signed informed consent
Currently receiving a stable antiretroviral regimen comprising of:
two licensed NRTIs including abacavir and/or didanosine
any licensed boosted protease inhibitor at any dose (excluding tipranavir*)
Undetectable plasma HIV RNA to less than 50 copies/mL for at least 24 weeks prior to screening
Availability of stored plasma with which to perform a tropism assay
CCR5 tropic HIV virus based on a tropism assay from a stored plasma sample
Willing to continue unchanged, or to modify antiretroviral therapy, in accordance with the randomisation assignment
No documented viral resistance to currently licensed HIV-1 protease inhibitors based either on previous HIV-1 genotypic resistance testing or in the judgement of the study investigators
No previous exposure to maraviroc or CCR5 receptor antagonists
Subjects in good health upon medical history, physical exam, and laboratory testing in the opinion of the investigator
Female subjects who are heterosexually active and of childbearing potential (i.e., not surgically sterile or at least two years post menopausal) must avoid becoming pregnancy as follows from screening through completion of the study using one or both of the following methods:
barrier contraceptives (condom, diaphragm with spermicide)
IUD PLUS a barrier contraceptive
Female subjects of childbearing potential must have a negative pregnancy test. Exclusion criteria
failure of current antiretroviral regimen due to virological failure
active opportunistic infection, malignancy or significant co-morbidities in the opinion of the investigator
pregnancy
current prohibited concomitant medication (as listed in section 4.1.4)
no available stored plasma sample predating their current antiretroviral regimen upon which a tropism assay can be performed
active HBV infection as evidenced by positive hepatitis B surface antigen
active hepatitis C virus infection as evidenced by positive HCV PCR or HCV antibody

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Prospective, Randomised Study to Assess Safety, Changes in Platelet Reactivity, Plasma Cardiac Biomarkers, Immunological and Metabolic Parameters in HIV-1 Infected Subjects Undergoing a Switch in Antiretroviral Therapy

Actual Study Start Date :

Sep 1, 2009

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Immediate switch Continue current boosted protease inhibitor Switch NRTI backbone to maraviroc 150 mg bid	Drug: Maraviroc Maraviroc 150 mg bid
Active Comparator: Continue current antiretroviral therapy Continue current antiretroviral regimen until week 12 then switch therapy as per arm 1.	Drug: Maraviroc maraviroc 150 mg bid switch 12 weeks later

Arm

Intervention/Treatment

Experimental: Immediate switch

Continue current boosted protease inhibitor Switch NRTI backbone to maraviroc 150 mg bid

Drug: Maraviroc

Maraviroc 150 mg bid

Active Comparator: Continue current antiretroviral therapy

Continue current antiretroviral regimen until week 12 then switch therapy as per arm 1.

Drug: Maraviroc

maraviroc 150 mg bid switch 12 weeks later

Outcome Measures

Primary Outcome Measures

Mean change from baseline in platelet reactivity between treatment arms at week 12 [48 weeks]

Secondary Outcome Measures

To assess for the following: Mean change over 24 weeks and mean difference at week 12 between study groups in plasma inflammatory and cardiac biomarkers and markers of immune activation [48 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

HIV-1 infected males or females
Between 18 and 65 years of age
Signed informed consent
Currently receiving a stable antiretroviral regimen comprising of:
two licensed NRTIs including abacavir and/or didanosine
any licensed boosted protease inhibitor at any dose (excluding tipranavir*)
Undetectable plasma HIV RNA to less than 50 copies/mL for at least 24 weeks prior to screening
Availability of stored plasma with which to perform a tropism assay
CCR5 tropic HIV virus based on a tropism assay from a stored plasma sample
Willing to continue unchanged, or to modify antiretroviral therapy, in accordance with the randomisation assignment
No documented viral resistance to currently licensed HIV-1 protease inhibitors based either on previous HIV-1 genotypic resistance testing or in the judgement of the study investigators
No previous exposure to maraviroc or CCR5 receptor antagonists
Subjects in good health upon medical history, physical exam, and laboratory testing in the opinion of the investigator
Female subjects who are heterosexually active and of childbearing potential (i.e., not surgically sterile or at least two years post menopausal) must avoid becoming pregnancy as follows from screening through completion of the study using one or both of the following methods:
barrier contraceptives (condom, diaphragm with spermicide)
IUD PLUS a barrier contraceptive
Female subjects of childbearing potential must have a negative pregnancy test

Exclusion Criteria:

failure of current antiretroviral regimen due to virological failure
active opportunistic infection, malignancy or significant co-morbidities in the opinion of the investigator
pregnancy
current prohibited concomitant medication (as listed in section 4.1.4)
no available stored plasma sample predating their current antiretroviral regimen upon which a tropism assay can be performed
active HBV infection as evidenced by positive hepatitis B surface antigen
active hepatitis C virus infection as evidenced by positive HCV PCR or HCV antibody.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Cork University Hospital	Cork	Ireland
2	Mater Misericordiae University Hospital	Dublin	Ireland
3	Imperial College Healthcare NHS Trust	London	United Kingdom	W2 1NY

Sponsors and Collaborators

Imperial College London
Mater Misericordiae University Hospital

Investigators

Principal Investigator: Alan Winston, MBChB, Imperial College London
Principal Investigator: Patrick Mallon, MBChB, UCD School of Medicine and Medical Sciences