The St. Marys and The Mater Switch Study (SMASH)

This study has been completed.
Sponsor:
Collaborator:
Mater Misericordiae University Hospital
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT00981773
First received: September 21, 2009
Last updated: May 20, 2014
Last verified: May 2011
  Purpose

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 Intervention Phase
HIV Infections
Drug: Maraviroc
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Mean change from baseline in platelet reactivity between treatment arms at week 12 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

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 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: September 2009
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00981773

Locations
Ireland
Cork University Hospital
Cork, Ireland
Mater Misericordiae University Hospital
Dublin, Ireland
United Kingdom
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
  More Information

No publications provided

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT00981773     History of Changes
Other Study ID Numbers: 1.0 18.6.2009
Study First Received: September 21, 2009
Last Updated: May 20, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Imperial College London:
HIV switch
HIV
treatment experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on October 20, 2014