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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Medical Research Council
Sponsor:
Collaborators:
Department for International Development, United Kingdom
Wellcome Trust
Medical Research Council
PENTA Foundation
Information provided by (Responsible Party):
Anna Griffiths, MRC, Medical Research Council
ClinicalTrials.gov Identifier:
NCT01825031
First received: January 7, 2013
Last updated: September 12, 2013
Last verified: September 2013

January 7, 2013
September 12, 2013
June 2013
August 2015   (final data collection date for primary outcome measure)
All-cause mortality over the first 24 weeks after starting ART [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01825031 on ClinicalTrials.gov Archive Site
  • 48 week mortality (all-cause) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: Week 0-48 ] [ Designated as safety issue: Yes ]
    • serious adverse events
    • grade 4 adverse events
    • adverse events leading to modification of ART or other study drugs
  • Hospital inpatient episodes and total days admitted [ Time Frame: Week 0-48 ] [ Designated as safety issue: Yes ]
  • Adherence to ART and acceptability of each strategy [ Time Frame: Week 0-48 ] [ Designated as safety issue: No ]
    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.
  • Endpoint relating to anti-infection intervention [ Time Frame: 0-48 weeks ] [ Designated as safety issue: No ]
    Incidence of tuberculosis (TB), cryptococcal and candida disease, severe bacterial infections
  • Endpoint relating to anti-malnutrition intervention [ Time Frame: 0-48 weeks ] [ Designated as safety issue: No ]
    BMI, weight and body fat assessed by bioimpedance analysis (BIA), height (in children) and grip strength
  • Endpoint relating to anti-HIV intervention [ Time Frame: 0-48 weeks ] [ Designated as safety issue: No ]
    Changes in CD4 cell count
Same as current
Not Provided
Not Provided
 
Reduction of EArly mortaLITY in HIV-infected Adults and Children Starting Antiretroviral Therapy
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Human Immunodeficiency Virus
  • Drug: Raltegravir
    400mg twice daily for the first 12 weeks only in addition to 3 standard ARVs
  • 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
  • Dietary Supplement: Ready to Use Supplementary Food
    2x92g packets daily of high energy, low protein lipid-based paste for 12 weeks
    Other Name: RUSF
  • 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
    Intervention: Drug: Raltegravir
  • 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.
    Interventions:
    • Drug: Fluconazole
    • Drug: Azithromycin
    • Drug: Albendazole
    • Drug: Isoniazid
  • 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.
    Intervention: Dietary Supplement: Ready to Use Supplementary Food
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1800
February 2016
August 2015   (final data collection date for primary outcome measure)

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).
Both
5 Years and older
No
Contact: Anna Griffiths reality@ctu.mrc.ac.uk
Kenya,   Malawi,   Uganda,   Zimbabwe
 
NCT01825031
ISRCTN43622374
Yes
Anna Griffiths, MRC, Medical Research Council
Anna Griffiths, MRC
  • Department for International Development, United Kingdom
  • Wellcome Trust
  • Medical Research Council
  • PENTA Foundation
Study Director: Diana M Gibb Medical Research Council
Medical Research Council
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP