Maraviroc Switch Collaborative Study (MARCH)

• ClinicalTrials.gov Identifier: NCT01384682
• Recruitment Status: Completed
• First Posted: June 29, 2011
• Last Update Posted: January 20, 2016
• Sponsor: Kirby Institute
• Collaborators: ViiV Healthcare; Pfizer
• Information provided by (Responsible Party): Kirby Institute

Study Description

Brief Summary:

MARCH is an international, multicentre trial planning to enroll 380 HIV-1 infected patients who are currently on 2N(t)RTI + PI/r regimen and virologically suppressed. Participants will be randomized (1:2:2) to one of three treatment groups: to continue their current treatment regimen, maraviroc dose at 150 mg twice daily with PI/r, or maraviroc at 300 mg twice daily with 2N(t)RTI. As the participants population have HIV RNA <200 copies/mL, the phenotypic assessment of tropism cannot be used to determine tropism, instead we will employ the genotypic assessment of tropism by sequencing the V3 loop of the HIV envelope. The main aim of this study is to investigate whether switching to maraviroc, in combination with either RTI or PI/r, is as good at keeping the HIV viral load undetectable as the combination of RTI with PI/r. The other aim is to see if switching to these combinations with maraviroc will improve some of the side effects that can be seen when people take combination therapy including RTI and PI/r.

The study hypothesis is that in stable, virologically suppressed (plasma HIV-RNA <200 copies/mL) patients with no history of prior virological failure, a switch to either MVC dosed at 300mg twice daily (bid) combined with the same 2N(t)RTI backbone regimen or MVC dosed at 150mg twice daily (bid) with the current PI/r (or 300mg bid at the discretion of the investigator if the PI/r is fosamprenavir/r) provides similar (non-inferior) antiretroviral efficacy compared to continuation of the current 2N(t)RTI + PI/r regimen.

Condition or disease	Intervention/treatment	Phase
HIV	Drug: Maraviroc	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 399 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomised, Openlabel Study Evaluating Efficacy and Safety of Maraviroc as a Switch for Either NRTI or 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 cART
• Study Start Date: August 2011
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
No Intervention: No change; continue their current cART regimen
Active Comparator: Replace N(t)RTI drugs with Maraviroc; Replace N(t)RTI drugs with MVC at a dose of 150mg bid (MVC 300mg bid can be used at the discretion of the Investigator if the PI/r is fosamprenavir/r) and continue the PI/r	Drug: Maraviroc; 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 bid except, Maraviroc 300mg bid 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 receive Maraviroc 300mg bid. Patients randomised to receive Maraviroc will be provided with bottles of Maraviroc which contain a 30-day supply.
Active Comparator: Replace PI/r drugs with Maraviroc; Replace PI/r drugs with MVC at a dose of 300mg bid and continue 2N(t)RTI.	Drug: Maraviroc; 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 bid except, Maraviroc 300mg bid 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 receive Maraviroc 300mg bid. Patients randomised to receive Maraviroc will be provided with bottles of Maraviroc which contain a 30-day supply.

Outcome Measures

Primary Outcome Measures :

1. The comparison of the switch arms to control arm of proportions of participants with HIV RNA <200 copies/mL 48 weeks after randomisation. [ Time Frame: 48 weeks after randomization ]

Secondary Outcome Measures :

1. Virological endpoints: proportion of participants with plasma HIV-1 RNA<50 copies/ml [ Time Frame: 48 weeks from randomization ]

   A number of secondary endpoints will be examined at or through to week 48 in this protocol. These will include, but not be limited to the following:

   Virologic; Immunologic and biomarkers; Clinical; Metabolic and body composition; Safety; Adherence; Quality of Life and Resistance endpoints.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Documented HIV-1 infection by a licensed diagnostic test at any time prior to study entry
• Age >18 years
• HIV-1 RNA <200 copies/mL plasma for at least 24 weeks
• Stable (>24 weeks) ART including two N(t)RTIs and a PI/r
• 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
• Provision of written, informed consent.

Exclusion Criteria:

• CXCR4 or CCR5/CXCR4 dual tropic HIV tropism or a non-reportable tropism result based on assessment using proviral DNA
• Anticipated need to modify current cART regimen for toxicity management in the next 6 months

• The following laboratory criteria,

  1. absolute neutrophil count (ANC) <750 cells/µL
  2. haemoglobin <8.0 g/dL
  3. platelet count <50,000 cells/µL
  4. serum AST, ALT >5 x upper limit of normal (ULN)
• Active hepatitis B co-infection
• Pregnant women or nursing mothers
• Current use of any prohibited medications as described in product specific information.
• Hypersensitivity to soy or peanuts
• Acute therapy for serious infection or other serious medical illness (in the judgement of the site Principal Investigator) requiring systemic treatment and/or hospitalisation
• Use of immunomodulators (e.g. systemic corticosteroids, recombinant interleukin-2, interferon) within 30 days prior to screening
• 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
• Patients unlikely to be able to remain in follow-up for the protocol-defined period
• Prisoners or subjects who are compulsorily detained (involuntary incarcerated).

Contacts and Locations

  Show 51 Study Locations

Sponsors and Collaborators

Kirby Institute

ViiV Healthcare

Pfizer

Investigators

• Principal Investigator: David A Cooper, AO; Kirby Institute, University of New South Wales

More Information

Additional Information:

Kirby Institute for infection and immunity in society homepage - click here for more information on the MARCH study. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Pett SL, Amin J, Horban A, Andrade-Villanueva J, Losso M, Porteiro N, Sierra Madero J, Belloso W, Tu E, Silk D, Kelleher A, Harrigan R, Clark A, Sugiura W, Wolff M, Gill J, Gatell J, Fisher M, Clarke A, Ruxrungtham K, Prazuck T, Kaiser R, Woolley I, Arnaiz JA, Cooper D, Rockstroh JK, Mallon P, Emery S; Maraviroc Switch (MARCH) Study Group. Maraviroc, as a Switch Option, in HIV-1-infected Individuals With Stable, Well-controlled HIV Replication and R5-tropic Virus on Their First Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Plus Ritonavir-boosted Protease Inhibitor Regimen: Week 48 Results of the Randomized, Multicenter MARCH Study. Clin Infect Dis. 2016 Jul 1;63(1):122-32. doi: 10.1093/cid/ciw207. Epub 2016 Apr 5.

Tu E, Swenson LC, Land S, Pett S, Emery S, Marks K, Kelleher AD, Kaye S, Kaiser R, Schuelter E, Harrigan R; MARCH Laboratory Group and the MARCH Study Group. Results of external quality assessment for proviral DNA testing of HIV tropism in the Maraviroc Switch collaborative study. J Clin Microbiol. 2013 Jul;51(7):2063-71. doi: 10.1128/JCM.00510-13. Epub 2013 Apr 17.

• Responsible Party: Kirby Institute
• ClinicalTrials.gov Identifier: NCT01384682 History of Changes
• Other Study ID Numbers: 2011-01-MAR
• First Posted: June 29, 2011
• Last Update Posted: January 20, 2016
• Last Verified: January 2016

Additional relevant MeSH terms:

Maraviroc; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; CCR5 Receptor Antagonists