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

April 19, 2016 updated by: Anna Griffiths, MRC

Reduction of Early mortALITY in HIV-infected African Adults and Children Starting Antiretroviral Therapy: a Randomised Controlled Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

1805

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Kenya
      • Eldoret, Kenya
        • Moi University Clinical Research Centre
      • Kilifi, Kenya
        • KEMRI Wellcome Trust Research Programme
  • Malawi
      • Blantyre, Malawi
        • University of Malawi
  • Uganda
      • Fort Portal, Uganda
        • Joint Clinical Research Centre, Fort Portal
      • Gulu, Uganda
        • Joint Clinical Research Centre, Gulu
      • Mbale, Uganda
        • Joint Clinical Research Centre, Mbale
      • Mbarara, Uganda
        • Joint Clinical Research Centre, Mbarara
  • Zimbabwe
      • Harare, Zimbabwe
        • University of Zimbabwe Clinical Research Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • RUSF

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
All-cause mortality over the first 24 weeks after starting ART
Time Frame: Week 24
Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
48 week mortality (all-cause)
Time Frame: Week 48
Week 48
Safety
Time Frame: Week 0-48
  • serious adverse events
  • grade 4 adverse events
  • adverse events leading to modification of ART or other study drugs
Week 0-48
Hospital inpatient episodes and total days admitted
Time Frame: Week 0-48
Week 0-48
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.
Week 0-48
Endpoint relating to anti-infection intervention
Time Frame: 0-48 weeks
Incidence of tuberculosis (TB), cryptococcal and candida disease, severe bacterial infections
0-48 weeks
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
0-48 weeks
Endpoint relating to anti-HIV intervention
Time Frame: 0-48 weeks
Changes in CD4 cell count
0-48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Anna Griffiths, MRC

Collaborators

Medical Research Council
Wellcome Trust
Department for International Development, United Kingdom
PENTA Foundation

Investigators

  • Study Director: Diana M Gibb, Medical Research Council

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2013

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

March 1, 2016

Study Registration Dates

First Submitted

January 7, 2013

First Submitted That Met QC Criteria

April 2, 2013

First Posted (Estimate)

April 5, 2013

Study Record Updates

Last Update Posted (Estimate)

April 20, 2016

Last Update Submitted That Met QC Criteria

April 19, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISRCTN43622374

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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