MARCH Renal Substudy - Full Text View

Purpose

Chronic kidney disease (CKD) is an emerging problem in patients with treated HIV. Antiretroviral therapy associated renal dysfunction has been predominantly described in terms of reduced glomerular filtration (eGFR). Proteinuria is a key component of CKD and may occur in the absence of significant reductions in eGFR. This substudy is an exploration of changes in urinary protein excretion in a randomised, open-label study to evaluate the efficacy and safety of 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).

Condition	Intervention	Phase
Proteinuria HIV	Drug: arm 1 nucleotide analogue reverse transcriptase inhibitors and boosted protease inhibitors Drug: Arm 2 boosted protease inhibitors and maraviroc Drug: Arm 3 nucleotide analogue reverse transcriptase inhibitors and maraviroc	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label
Official Title:	Maraviroc Switch Collaborative Study Renal Substudy

Resource links provided by NLM:

Further study details as provided by Kirby Institute:

Primary Outcome Measures:

changes in proteinuria and albuminuria between baseline and week 96 [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
To compare the change in protein and albumin excretion as measured by the urine PCR and ACR through the kidneys between the randomised and standard of care (control) arm of MARCH.

Secondary Outcome Measures:

changes in renal tubular function between baseline and week 96 [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
To evaluate the following aspects of renal function at baseline and changes within and between study groups:
- Tubular function defined as proximal tubular function; ascending thick loop of Henle; distal tubular function; volume and renal potassium handling;
- Non-tubular function i.e. eGFR; Urine albumin:creatinine ratio;
- Determine factors associated with renal dysfunction within the cohort e.g. demographics, HIV related, HIV-treatment related, co-morbidities, concomitant medication (such as ACE inhibitors and ARB; PI/r co-administered with TDF); TDF use;


Enrollment:	76
Study Start Date:	June 2012
Study Completion Date:	December 2015
Primary Completion Date:	December 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: NRTI + PI arm 1	Drug: arm 1 nucleotide analogue reverse transcriptase inhibitors and boosted protease inhibitors NRTI + PI Other Names: tenofovir emtricitabine zidovudine abacavir lamivudine atazanavir lopinavir darunavir fosamprenavir ritonavir
Active Comparator: PI + maraviroc arm 2	Drug: Arm 2 boosted protease inhibitors and maraviroc PI + maraviroc Other Names: maraviroc atazanavir lopinavir darunavir fosamprenavir ritonavir
Active Comparator: NRTI + maraviroc arm 3	Drug: Arm 3 nucleotide analogue reverse transcriptase inhibitors and maraviroc NRTI + maraviroc Other Names: maraviroc tenofovir emtricitabine zidovudine abacavir lamivudine

Detailed Description:

The aim of this substudy of MARCH is to characterize the changes in protein and salt excretion through the kidney utilising the randomised arms of the parent study MARCH. The investigators hypothesize there will be an improvement in proteinuria in those switching to maraviroc containing regimens.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Provision of written, informed consent for participation in the substudy
Enrolled into the substudy either at or before the week 0 visit of the main study

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: NCT01637259

Locations


Argentina
Hospital Italiano de Buenos Aires
Buenos Aires, Ciudad de Buenos Aires, Argentina, C1181ACH
Hospital General de Agudos J M Ramos Mejia
Buenos Aires, Ciudad de Buenos Aires, Argentina, C1221ADC
Fundación IDEAA
Buenos Aires, Ciudad de Buenos Aires, Argentina, C1405CKC
Australia, New South Wales
St. Vincent's Hospital
Sydney, New South Wales, Australia, 2010
Australia, Queensland
Brisbane Sexual Health and HIV Service
Brisbane, Queensland, Australia, 4000
Canada, Alberta
Southern Alberta Clinic
Calgary, Alberta, Canada, T2R OX7
Canada, Ontario
University Health Network - Toronto General Hospital
Toronto, Ontario, Canada, M5G 2N2
Canada, Quebec
Clinic Opus/Lori
Montreal, Quebec, Canada, H3A 1T1
Germany
Klinikum der Universitat Zu Koln
Cologne, Germany, 50937
Universitätsklinikum Düsseldorf, Klinik für Gastroenterologie, Hepatologie und Infektiologie, MX-Ambulanz
Dusseldorf, Germany, 40225
Japan
Nagoya Medical Center
Nagoya, Japan, 460-0001
Mexico
Instituto Nacional de Ciencias Medicas y Nutriciòn Salvador Zubiran
Mexico City, Tlalpan DF, Mexico, 14000
Thailand
Chulalongkorn University Hospital
Bangkok, Thailand, 10330
United Kingdom
Western General Hospital
Edinburgh, Lothian, United Kingdom
Brighton & Sussex University NHS Trust
Brighton, Sussex, United Kingdom

Sponsors and Collaborators

Kirby Institute

Investigators


Principal Investigator:	Waldo Belloso, MD	Hospital Italiano de Buenos Aires
Principal Investigator:	Mark Kelly, MD	Brisbane Sexual Health and HIV Service

More Information


Responsible Party:	Kirby Institute
ClinicalTrials.gov Identifier:	NCT01637259 History of Changes
Other Study ID Numbers:	MARCH-Kirby renal
Study First Received:	June 27, 2012
Last Updated:	January 18, 2016
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration Thailand: Ministry of Public Health Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Japan: Ministry of Health, Labor and Welfare Canada: Health Canada Mexico: Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Kirby Institute:


proteinuria HIV

Additional relevant MeSH terms:


Proteinuria Urination Disorders Urologic Diseases Urological Manifestations Signs and Symptoms Ritonavir Lopinavir Atazanavir Sulfate Darunavir HIV Protease Inhibitors Fosamprenavir Tenofovir Zidovudine Emtricitabine Lamivudine	Maraviroc Abacavir Protease Inhibitors Reverse Transcriptase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Nucleic Acid Synthesis Inhibitors Antimetabolites CCR5 Receptor Antagonists

ClinicalTrials.gov processed this record on September 23, 2016

MARCH Renal Substudy (MARCHrenal)