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Trial registered on ANZCTR


Registration number
ACTRN12611000816954
Ethics application status
Approved
Date submitted
13/07/2011
Date registered
3/08/2011
Date last updated
29/08/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised, open-label study to evaluate the efficacy and safety of maraviroc (MVC) as a switch for either nucleoside or nucleotide analogue reverse transcriptase inhibitors (N(t)RTI) or boosted protease inhibitors (PI/r) in HIV-1 infected individuals with stable, well-controlled plasma HIV-RNA while taking their first N(t)RTI + PI/r regimen of combination antiretroviral therapy (cART): MARCH study
Scientific title
A randomised, open-label study to evaluate the efficacy and safety of maraviroc (MVC) as a switch for either nucleoside or nucleotide analogue reverse transcriptase inhibitors (N(t)RTI) or boosted protease inhibitors (PI/r) in HIV-1 infected individuals with stable, well-controlled plasma HIV-RNA while taking their first N(t)RTI + PI/r regimen of combination antiretroviral therapy (cART)
Secondary ID [1] 262627 0
KI-MARCH-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV 268323 0
Condition category
Condition code
Inflammatory and Immune System 268454 268454 0 0
Other inflammatory or immune system disorders
Infection 268490 268490 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Maraviroc is a marketed drug for the treatment of HIV-infection. Maraviroc will be supplied in two different oral dose forms. 150mg and 300mg given twice a day. The drug will be dosed according to the recommendations in the product label i.e. with PI/r the dose is 150mg twice daily except, Miraviroc 300mg twice daily can be used at the discretion of the investigator if the PI/r is fosamprenavir/r, those randomised to the 2N(t)RTI arm, will recieve Maraviroc 300mg twice daily. Patients randomised to receive Miraviroc will be provided with bottles of Miravoroc at time points weeks 4, 12, 24, 36, 48, 60, 72, and 84. Each bottle contains a 30-day supply, however at the week 12 visit and ownards, the participant will receive 3 bottles.

There are 3 treatment arms in this study:
Arm 1 - No change i.e. continue their current cART regimen
Arm 2 - Replace N(t)RTI drugs with MVC at a dose of 150mg twice daily (MVC 300mg twice daily can be used at the discretion of the Investigator if the PI/r is fosamprenavir/r) and continue the PI/r
Arm 3 - Replace PI/r drugs with MVC at a dose of 300mg twice daily and continue 2N(t)RTI.

Treatment will continue until the last randomised participant has completed 96 weeks of follow-up or has permanently withdrawn from follow-up.
Intervention code [1] 266975 0
Treatment: Drugs
Comparator / control treatment
No change: participants shall remain on their current cART regimen
Control group
Active

Outcomes
Primary outcome [1] 269212 0
The comparison of the switch arms to control arm of proportions of participants with HIV RNA <200 copies/mL
Timepoint [1] 269212 0
48 weeks after randomization
Secondary outcome [1] 279131 0
Virologic endpoints
-Proportion of participants with plasma HIV-1 RNA <50 copies/mL
-Time to virological failure (defined as plasma HIV-1 RNA 200 copies/mL on randomised therapy, on two occasions at least seven days apart)
-Time to loss of virological response, as defined by virological failure, permanent randomised treatment discontinuation, new AIDS defining illness, death or withdrawal from study
-Changes from baseline in log plasma HIV-1 RNA copies/mL
-Frequency of plasma HIV-1 RNA blips (defined as a plasma viral load result >200 copies/mL on randomised therapy following a previous result <200 copies/mL, with a follow up result <200 copies/mL at least seven days after the >200 copies/mL reading, in the absence of a change of any component of the ART regimen).
Timepoint [1] 279131 0
48 weeks after randomization
Secondary outcome [2] 279179 0
Immunologic and biomarker endpoints
-Changes from baseline in absolute and percentage CD4+ and CD8+T cells
-Changes from baseline in selected soluble markers of immune activation/coagulation.
Timepoint [2] 279179 0
48 weeks after randomization
Secondary outcome [3] 279180 0
Clinical endpoints
-Rate of opportunistic disease (AIDS) or death
-Rates of serious non AIDS defining illness and non AIDS related mortality.
Timepoint [3] 279180 0
48 weeks after randomization
Secondary outcome [4] 279181 0
Metabolic and body composition endpoints
-Changes from baseline in fasting lipids (TC, LDL, HDL and TG)
-Changes in absolute CVD risk assessment using the Framingham risk equation
-Changes from baseline in fasting glucose and insulin
-Rates of initiation or changes in existing lipid lowering therapies
-Changes from baseline in anthropometric changes derived from Dual energy X ray absorptiometry (DXA) scanning of peripheral and central adipose tissue
-Changes from baseline in bone mineral density and body fat as measured by DXA
-Changes in 10 year fracture risk using the FRAX algorithm
-Changes from baseline in markers of bone turnover.
Timepoint [4] 279181 0
48 weeks after randomization
Secondary outcome [5] 279182 0
Safety
-Changes from baseline in selected serum biochemical parameters, including changes in estimated glomerular filtration rate (GFR)
Timepoint [5] 279182 0
48 weeks after randomization
Secondary outcome [6] 279183 0
Adherence
-Self reported adherence to randomised study medications.
Timepoint [6] 279183 0
48 weeks after randomization
Secondary outcome [7] 279184 0
Quality of Life
Change from baseline health status scores as measured by the SF12 questionnaire.
Timepoint [7] 279184 0
48 weeks after randomization
Secondary outcome [8] 279185 0
Resistance endpoints
-Patterns of genotypic resistance at virological failure.
Timepoint [8] 279185 0
48 weeks after randomization

Eligibility
Key inclusion criteria
1. Documented HIV-1 infection by a licensed diagnostic test at any time prior to study entry
2. Age >18 years
3. HIV-1 RNA <200 copies/mL plasma for at least 24 weeks
4. Stable (>24 weeks) ART including two N(t)RTIs and a PI/r
5. No evidence of any primary HIV genotypic mutations in HIV reverse transcriptase or protease for all patients with available resistance testing results conducted prior to cART and/or during viral rebound/failure
6. Provision of written, informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. CXCR4 or CCR5/CXCR4 dual tropic HIV tropism or a non-reportable tropism result based on assessment using proviral DNA
2. Anticipated need to modify current cART regimen for toxicity management in the next 6 months
3. The following laboratory criteria,
a. absolute neutrophil count (ANC) <750 cells/micro L
b. haemoglobin <8.0 g/dL
c. platelet count <50,000 cells/micro L
d. serum AST, ALT >5 x upper limit of normal (ULN)
4. Active hepatitis B co-infection
5. Pregnant women or nursing mothers
6. Current use of any prohibited medications as described in product specific information.
7. Hypersensitivity to soy or peanuts
8. Acute therapy for serious infection or other serious medical illness (in the judgement of the site Principal Investigator) requiring systemic treatment and/or hospitalisation
9. Use of immunomodulators (e.g. systemic corticosteroids, recombinant interleukin-2, interferon) within 30 days prior to screening
10. Patients with current alcohol or illicit substance use that in the opinion of the site Principal Investigator would conflict with any aspect of the conduct of the study
11. Patients unlikely to be able to remain in follow-up for the protocol-defined period
12. Prisoners or subjects who are compulsorily detained (involuntary incarcerated).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
26/08/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
560
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 3710 0
Argentina
State/province [1] 3710 0
Country [2] 3711 0
Canada
State/province [2] 3711 0
Country [3] 3712 0
Chile
State/province [3] 3712 0
Country [4] 3713 0
Germany
State/province [4] 3713 0
Country [5] 3714 0
Ireland
State/province [5] 3714 0
Country [6] 3715 0
Israel
State/province [6] 3715 0
Country [7] 3716 0
Mexico
State/province [7] 3716 0
Country [8] 3717 0
Peru
State/province [8] 3717 0
Country [9] 3718 0
Spain
State/province [9] 3718 0
Country [10] 3719 0
United Kingdom
State/province [10] 3719 0
Country [11] 3720 0
France
State/province [11] 3720 0
Country [12] 3721 0
Japan
State/province [12] 3721 0

Funding & Sponsors
Funding source category [1] 267449 0
Commercial sector/Industry
Name [1] 267449 0
Pfizer Inc., a Delaware Corporation
Country [1] 267449 0
United States of America
Primary sponsor type
University
Name
University of New South Wales, Kirby Institute
Address
Cliffbrook Campus
45 Beach Street
Coogee
New South Wales 2034
Country
Australia
Secondary sponsor category [1] 266625 0
None
Name [1] 266625 0
Address [1] 266625 0
Country [1] 266625 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269415 0
St. Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 269415 0
Ethics committee country [1] 269415 0
Australia
Date submitted for ethics approval [1] 269415 0
23/05/2011
Approval date [1] 269415 0
Ethics approval number [1] 269415 0
11/065

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32875 0
Address 32875 0
Country 32875 0
Phone 32875 0
Fax 32875 0
Email 32875 0
Contact person for public queries
Name 16122 0
Dr Sarah L. Pett
Address 16122 0
Kirby Institute, Faculty of Medicine, UNSW
Cliffbrook Campus, Building CC4, Level 2
45 Beach Street
Coogee
NSW 2034
Country 16122 0
Australia
Phone 16122 0
+61-2-9385-0900
Fax 16122 0
+61.2.9385.0910
Email 16122 0
spett@kirby.unsw.edu.au
Contact person for scientific queries
Name 7050 0
Prof. David A. Cooper
Address 7050 0
Kirby Institute, Faculty of Medicine, UNSW
Cliffbrook Campus, Building CC4, Level 2
45 Beach Street
Coogee
NSW 2034
Country 7050 0
Australia
Phone 7050 0
+61.2.8382.4904
Fax 7050 0
+61.2.9385.0910
Email 7050 0
dcooper@kirby.unsw.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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