Reduction of EArly mortaLITY in HIV-infected Adults and Children Starting Antiretroviral Therapy
NCT ID: NCT01825031
Last Updated: 2016-04-20
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE3
1805 participants
INTERVENTIONAL
2013-06-30
2016-03-31
Brief Summary
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(i) increasing the potency of ART with a 12 week induction period using 4 antiretroviral drugs from 3 classes
(ii) augmented prophylaxis against opportunistic/bacterial infections and helminths for 12 weeks
(iii) macronutrient intervention using ready-to-use supplementary food for 12 weeks.
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Detailed Description
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The trial will have a factorial design with 3 randomisations, each to address one of the potential approaches to reduce early mortality in adults and children initiating ART with low CD4, namely:
1. Raltegravir for 12 weeks from ART initiation in addition to 3 standard ART (3-drug 2-class) versus standard of care first-line 3-drug 2-class ART (choice according to national guidelines for ART initiation);
2. Immediate enhanced opportunistic infections (OI) prophylaxis with isoniazid/pyridoxine and cotrimoxazole, plus 12 weeks fluconazole, 5 days azithromycin and a single dose of albendazole versus cotrimoxazole prophylaxis alone for the first 12 weeks followed by isoniazid and any prophylaxis and/or treatment prescribed at screening
3. supplementation with Ready to Use Supplementary Food (RUSF) for 12 weeks versus standard of care nutritional support to those with poor nutritional status according to local guidelines.
All participants will receive cotrimoxazole throughout the trial.
The primary objective of the trial is to identify effective, safe and acceptable interventions to reduce early mortality (all-cause) in HIV-infected adults, adolescents, and older children (5 years or more) initiating ART.
Conditions
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Study Design
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RANDOMIZED
FACTORIAL
TREATMENT
NONE
Study Groups
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Antiretroviral Therapy
Raltegravir twice daily for 12 weeks from antiretroviral therapy (ART) initiation in addition to 3 standard ARVs (2NRTIs/1NNRTI) compared with 3 standard ARVs
Raltegravir
400mg twice daily for the first 12 weeks only in addition to 3 standard ARVs
Opportunistic Infection (OI) Prophylaxis
Immediate isoniazid/pyridoxine and cotrimoxazole, plus 12 weeks fluconazole, 5 days azithromycin and a single dose of albendazole compared with immediate cotrimoxazole (if not already taking this) in all patients plus (not malawi)isoniazid/pyridoxine after 12 weeks.
Fluconazole
100mg once daily for 12 weeks
Azithromycin
500mg once daily for 5 days
Albendazole
a single dose 400mg
Isoniazid
300mg taken immediately in combination with cotrimoxazole
Nutritional Support
Supplementation with Ready to Use Supplementary Food (RUSF) for 12 weeks compared with supplementation for those with severe malnutrition as local practice.
Ready to Use Supplementary Food
2x92g packets daily of high energy, low protein lipid-based paste for 12 weeks
Interventions
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Raltegravir
400mg twice daily for the first 12 weeks only in addition to 3 standard ARVs
Fluconazole
100mg once daily for 12 weeks
Azithromycin
500mg once daily for 5 days
Albendazole
a single dose 400mg
Isoniazid
300mg taken immediately in combination with cotrimoxazole
Ready to Use Supplementary Food
2x92g packets daily of high energy, low protein lipid-based paste for 12 weeks
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Documented HIV infection by HIV ELISA or HIV rapid test
* Naive to ART
* CD4 T-cell count \<100 cells/mm3 on blood test taken at screening for REALITY
* Results of screening haematology and biochemistry tests available and no contraindications to planned ART according to national guidelines
* Patient/carer provide informed consent (and children \<18 years assent, as appropriate according to their age and knowledge of HIV status)
The lower age limit is because CD4 counts are less reliable predictors of immunodeficiency under 5 years: CD4 counts are recommended by guidelines in older children.
No patient with a CD4 count above 100 cells/mm3 should have ART delayed in order to subsequently meet eligibility criteria. Rather, patients eligible for REALITY will be those testing HIV positive for the first time with a low CD4 count (i.e. those delaying presentation to care), or those who have defaulted before initiating ART and only return to care at an advanced stage of immuno-deficiency.
Exclusion Criteria
* Pregnant or breastfeeding or intending to become pregnant during the first 12 weeks of the study
* Ever known to have previously received single-dose nevirapine for prevention of mother-to-child transmission (mother or child).
5 Years
ALL
No
Sponsors
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Department for International Development, United Kingdom
OTHER_GOV
Wellcome Trust
OTHER
Medical Research Council
OTHER_GOV
PENTA Foundation
NETWORK
Anna Griffiths, MRC
OTHER_GOV
Responsible Party
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Anna Griffiths, MRC
Trial Manager
Principal Investigators
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Diana M Gibb
Role: STUDY_DIRECTOR
Medical Research Council
Locations
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Moi University Clinical Research Centre
Eldoret, , Kenya
KEMRI Wellcome Trust Research Programme
Kilifi, , Kenya
University of Malawi
Blantyre, , Malawi
Joint Clinical Research Centre, Fort Portal
Fort Portal, , Uganda
Joint Clinical Research Centre, Gulu
Gulu, , Uganda
Joint Clinical Research Centre, Mbale
Mbale, , Uganda
Joint Clinical Research Centre, Mbarara
Mbarara, , Uganda
University of Zimbabwe Clinical Research Centre
Harare, , Zimbabwe
Countries
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References
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Kelly C, Tinago W, Alber D, Hunter P, Luckhurst N, Connolly J, Arrigoni F, Garcia Abner A, Kamn'gona R, Sheha I, Chammudzi M, Jambo K, Mallewa J, Rapala A, Mallon PWG, Mwandumba H, Klein N, Khoo S. Inflammatory pathways amongst people living with HIV in Malawi differ according to socioeconomic status. PLoS One. 2021 Aug 25;16(8):e0256576. doi: 10.1371/journal.pone.0256576. eCollection 2021.
Kelly C, Tinago W, Alber D, Hunter P, Luckhurst N, Connolly J, Arrigoni F, Abner AG, Kamngona R, Sheha I, Chammudzi M, Jambo K, Mallewa J, Rapala A, Heyderman RS, Mallon PWG, Mwandumba H, Walker AS, Klein N, Khoo S. Inflammatory Phenotypes Predict Changes in Arterial Stiffness Following Antiretroviral Therapy Initiation. Clin Infect Dis. 2020 Dec 3;71(9):2389-2397. doi: 10.1093/cid/ciaa186.
Kityo C, Szubert AJ, Siika A, Heyderman R, Bwakura-Dangarembizi M, Lugemwa A, Mwaringa S, Griffiths A, Nkanya I, Kabahenda S, Wachira S, Musoro G, Rajapakse C, Etyang T, Abach J, Spyer MJ, Wavamunno P, Nyondo-Mipando L, Chidziva E, Nathoo K, Klein N, Hakim J, Gibb DM, Walker AS, Pett SL; REALITY trial team. Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial. PLoS Med. 2018 Dec 4;15(12):e1002706. doi: 10.1371/journal.pmed.1002706. eCollection 2018 Dec.
Mallewa J, Szubert AJ, Mugyenyi P, Chidziva E, Thomason MJ, Chepkorir P, Abongomera G, Baleeta K, Etyang A, Warambwa C, Melly B, Mudzingwa S, Kelly C, Agutu C, Wilkes H, Nkomani S, Musiime V, Lugemwa A, Pett SL, Bwakura-Dangarembizi M, Prendergast AJ, Gibb DM, Walker AS, Berkley JA; REALITY trial team. Effect of ready-to-use supplementary food on mortality in severely immunocompromised HIV-infected individuals in Africa initiating antiretroviral therapy (REALITY): an open-label, parallel-group, randomised controlled trial. Lancet HIV. 2018 May;5(5):e231-e240. doi: 10.1016/S2352-3018(18)30038-9. Epub 2018 Apr 10.
Other Identifiers
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ISRCTN43622374
Identifier Type: -
Identifier Source: org_study_id
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