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Reduction of EArly mortaLITY in HIV-infected Adults and Children Starting Antiretroviral Therapy (REALITY)

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ClinicalTrials.gov Identifier: NCT01825031
Recruitment Status : Completed
First Posted : April 5, 2013
Last Update Posted : April 20, 2016
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief Summary:

A randomised controlled trial to investigate three methods to reduce early mortality in adults, adolescents and children aged 5 years or older starting antiretroviral therapy (ART) with severe immuno-deficiency. The three methods are:

(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.


Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Drug: Raltegravir Drug: Fluconazole Drug: Azithromycin Drug: Albendazole Drug: Isoniazid Dietary Supplement: Ready to Use Supplementary Food Phase 3

Detailed Description:

REALITY is a open-label randomised trial of 1800 adults, adolescents and children aged 5 years or more with low CD4 counts about to initiate ART.

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1805 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reduction of Early mortALITY in HIV-infected African Adults and Children Starting Antiretroviral Therapy: a Randomised Controlled Trial
Study Start Date : June 2013
Primary Completion Date : March 2016
Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: 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
Drug: Raltegravir
400mg twice daily for the first 12 weeks only in addition to 3 standard ARVs
Experimental: 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.
Drug: Fluconazole
100mg once daily for 12 weeks
Drug: Azithromycin
500mg once daily for 5 days
Drug: Albendazole
a single dose 400mg
Drug: Isoniazid
300mg taken immediately in combination with cotrimoxazole
Experimental: Nutritional Support
Supplementation with Ready to Use Supplementary Food (RUSF) for 12 weeks compared with supplementation for those with severe malnutrition as local practice.
Dietary Supplement: Ready to Use Supplementary Food
2x92g packets daily of high energy, low protein lipid-based paste for 12 weeks
Other Name: RUSF


Outcome Measures

Primary Outcome Measures :
  1. All-cause mortality over the first 24 weeks after starting ART [ Time Frame: Week 24 ]

Secondary Outcome Measures :
  1. 48 week mortality (all-cause) [ Time Frame: Week 48 ]
  2. Safety [ Time Frame: Week 0-48 ]
    • serious adverse events
    • grade 4 adverse events
    • adverse events leading to modification of ART or other study drugs

  3. Hospital inpatient episodes and total days admitted [ Time Frame: Week 0-48 ]
  4. Adherence to ART and acceptability of each strategy [ Time Frame: Week 0-48 ]
    Adherence to ART, OI drugs and RUSF will be assessed in all participants at each visit by pill counts and short nurse-administered questions. Every 12 weeks, a more detailed adherence questionnaire will be adminstered.

  5. Endpoint relating to anti-infection intervention [ Time Frame: 0-48 weeks ]
    Incidence of tuberculosis (TB), cryptococcal and candida disease, severe bacterial infections

  6. Endpoint relating to anti-malnutrition intervention [ Time Frame: 0-48 weeks ]
    BMI, weight and body fat assessed by bioimpedance analysis (BIA), height (in children) and grip strength

  7. Endpoint relating to anti-HIV intervention [ Time Frame: 0-48 weeks ]
    Changes in CD4 cell count


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged 5 years or older
  • 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:

  • Contraindications to any proposed antiretroviral drugs (including integrase inhibitors), isoniazid, fluconazole, albendazole or azithromycin
  • 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).
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01825031


Locations
Kenya
Moi University Clinical Research Centre
Eldoret, Kenya
KEMRI Wellcome Trust Research Programme
Kilifi, Kenya
Malawi
University of Malawi
Blantyre, Malawi
Uganda
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
Zimbabwe
University of Zimbabwe Clinical Research Centre
Harare, Zimbabwe
Sponsors and Collaborators
Anna Griffiths, MRC
Department for International Development, United Kingdom
Wellcome Trust
Medical Research Council
PENTA Foundation
Investigators
Study Director: Diana M Gibb Medical Research Council
More Information

Responsible Party: Anna Griffiths, MRC, Trial Manager, Medical Research Council
ClinicalTrials.gov Identifier: NCT01825031     History of Changes
Other Study ID Numbers: ISRCTN43622374
First Posted: April 5, 2013    Key Record Dates
Last Update Posted: April 20, 2016
Last Verified: April 2016

Keywords provided by Anna Griffiths, MRC, Medical Research Council:
HIV

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Raltegravir Potassium
Fluconazole
Isoniazid
Albendazole
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs