AzTrials
AzTrials

Human Immunodeficiency VirusPhase 3REALITYNCT01825031

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

A Phase 3 study testing Raltegravir, Fluconazole and Azithromycin in people with Human Immunodeficiency Virus, run by Anna Griffiths, MRC at 8 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 5 years and older
Conditions the study is for
Human Immunodeficiency Virus
What is being tested?
Raltegravir, Fluconazole and Azithromycin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,805 participants
Where
8 sitesin 4 countries
Study dates
Jun 2013to Mar 2016
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 5 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).

Trial locations and contacts

8 sites in 4 countries.

8 sites in 4 countries

Uganda4 sites

  • Joint Clinical Research Centre, Fort Portal

    Fort Portal

  • Joint Clinical Research Centre, Gulu

    Gulu

  • Joint Clinical Research Centre, Mbale

    Mbale

  • Joint Clinical Research Centre, Mbarara

    Mbarara

Other trials in Uganda

Kenya2 sites

  • Moi University Clinical Research Centre

    Eldoret

  • KEMRI Wellcome Trust Research Programme

    Kilifi

Other trials in Kenya

Malawi1 site

  • University of Malawi

    Blantyre

Other trials in Malawi

Zimbabwe1 site

  • University of Zimbabwe Clinical Research Centre

    Harare

Other trials in Zimbabwe

About this study

Official title: 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.

Read the 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.

Being tested
Raltegravir, Fluconazole, Azithromycin, Albendazole, Isoniazid
Keywords
HIV
Medical subject headings
Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RaltegravirDrug

    400mg twice daily for the first 12 weeks only in addition to 3 standard ARVs

  • FluconazoleDrug

    100mg once daily for 12 weeks

  • AzithromycinDrug

    500mg once daily for 5 days

  • AlbendazoleDrug

    a single dose 400mg

  • IsoniazidDrug

    300mg taken immediately in combination with cotrimoxazole

  • Ready to Use Supplementary FoodDietary supplement

    Also called RUSF

    2x92g packets daily of high energy, low protein lipid-based paste for 12 weeks

Study groups in NCT01825031
Study groupRoleWhat they receive
Antiretroviral TherapyExperimentalRaltegravir twice daily for 12 weeks from antiretroviral therapy (ART) initiation in addition to 3 standard ARVs (2NRTIs/1NNRTI) compared with 3 standard ARVs
Receives: Drug: Raltegravir
Opportunistic Infection (OI) ProphylaxisExperimentalImmediate 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.
Receives: Drug: Fluconazole; Drug: Azithromycin; Drug: Albendazole; Drug: Isoniazid
Nutritional SupportExperimentalSupplementation with Ready to Use Supplementary Food (RUSF) for 12 weeks compared with supplementation for those with severe malnutrition as local practice.
Receives: Dietary Supplement: Ready to Use Supplementary Food

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. All-cause mortality over the first 24 weeks after starting ART

    Measured: Week 24

Secondary outcomes (7)

  1. 48 week mortality (all-cause)

    Measured: Week 48

  2. Safety

    • serious adverse events
    • grade 4 adverse events
    • adverse events leading to modification of ART or other study drugs

    Measured: Week 0-48

  3. Hospital inpatient episodes and total days admitted

    Measured: Week 0-48

  4. Adherence to ART and acceptability of each strategy

    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.

    Measured: Week 0-48

  5. Endpoint relating to anti-infection intervention

    Incidence of tuberculosis (TB), cryptococcal and candida disease, severe bacterial infections

    Measured: 0-48 weeks

  6. Endpoint relating to anti-malnutrition intervention

    BMI, weight and body fat assessed by bioimpedance analysis (BIA), height (in children) and grip strength

    Measured: 0-48 weeks

  7. Endpoint relating to anti-HIV intervention

    Changes in CD4 cell count

    Measured: 0-48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Apr 2013 (estimated)
  2. Study startJun 2013
  3. Primary completionMar 2016
  4. Study completionMar 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
1,805 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01825031
Sponsor's protocol ID
ISRCTN43622374
Acronym
REALITY
Status last verified
Apr 2016
First submitted
7 Jan 2013
Last updated
20 Apr 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 34432828

  • 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.

    PubMed 32103268

  • 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.

    PubMed 30513108

  • 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.

    PubMed 29653915

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Raltegravir, Fluconazole and Azithromycin in people with Human Immunodeficiency Virus, run by Anna Griffiths, MRC at 8 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Uganda, Kenya, Malawi, Zimbabwe. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

All-cause mortality over the first 24 weeks after starting ART (time frame: Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01825031, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in