NCT01924286

Brief Summary

Tuberculosis (TB) is the most common opportunistic infection amongst HIV-infected patients starting antiretroviral therapy (ART) in developing countries and thus the most frequent form of immune reconstitution inflammatory syndrome (IRIS). Paradoxical TB-IRIS occurs in 8- 43% of patients starting ART while on TB treatment and results in morbidity, hospitalisation, consumes health care resources and TB-IRIS may be fatal. We have previously demonstrated in a clinical trial that prednisone reduces morbidity when used for treatment of paradoxical TB-IRIS. This trial is a double-blind placebo-controlled trial of prophylactic prednisone (40mg/day for 2 weeks followed by 20mg/day for 2 weeks, started on the same day as ART) in patients with TB who are identified as being at high risk for paradoxical TB-IRIS (starting ART within 30 days of initiating TB treatment and CD4 \< 100/μL). The trial will enroll 240 participants, randomised 1:1 (prednisone:placebo). The primary endpoint is development of paradoxical TB-IRIS, defined using international consensus case definitions. Secondary endpoints include time to IRIS event, severity of IRIS, quality of life assessment, mortality and corticosteroids adverse events. The trial is powered to determine a reduction in TB-IRIS events.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
240

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Aug 2013

Typical duration for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 12, 2013

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 16, 2013

Completed
14 days until next milestone

Study Start

First participant enrolled

August 30, 2013

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2016

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2017

Completed
Last Updated

January 19, 2018

Status Verified

January 1, 2018

Enrollment Period

2.6 years

First QC Date

August 12, 2013

Last Update Submit

January 18, 2018

Conditions

Immune Reconstitution Inflammatory SyndromeHIVTuberculosis

Keywords

HIVTuberculosisImmune reconstitution inflammatory syndromeHighly active antiretroviral therapyGlucocorticoidsPrednisonePreventive therapy

Outcome Measures

Primary Outcomes (1)

  • Development of paradoxical TB-IRIS

    The development of paradoxical TB-IRIS within 12 weeks of starting ART (defined using the International Network for the Study of HIV-associated IRIS (INSHI) consensus case definition)

    12 weeks

Secondary Outcomes (19)

  • Time to IRIS event

    12 weeks

  • Severity of IRIS events

    12 weeks

  • Duration of TB-IRIS event

    Average 8-12 weeks from onset

  • Mortality attributed to TB and TB-IRIS

    12 weeks

  • All-cause mortality

    12 weeks

  • +14 more secondary outcomes

Other Outcomes (4)

  • Quality of life assessment

    12 weeks

  • Quality of life assessment

    12 weeks

  • Quality of life assessment

    12 weeks

  • +1 more other outcomes

Study Arms (2)

Prednisone

EXPERIMENTAL

Prednisone oral tablets 40mg daily for 2 weeks followed by 20mg daily for 2 weeks

Drug: Prednisone

Placebo

PLACEBO COMPARATOR

Placebo oral tablets 40mg daily for 2 weeks followed by 20mg daily for 2 weeks

Drug: Placebo

Interventions

PrednisoneDRUG
Also known as: Trolic
Prednisone
PlaceboDRUG
Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • HIV-infected HIV infection will be confirmed by two different rapid tests (as per South African national Department of Health guidelines) and an HIV viral load test.
  • CD4 count \< 100/μL One CD4 count taken within 3 months prior to enrolment less than 100/μL will qualify, even if other CD4 counts are greater than 100/μL
  • Confirmed diagnosis of TB (smear, culture, Xpert MTB/RIF test or compatible histology) or strong clinical and radiological evidence of TB with symptomatic response to TB treatment
  • On TB treatment for less than 30 days prior to study entry.
  • Eligible for ART and patient consents to starting ART within 30 days of starting TB treatment.
  • Written informed consent for trial

You may not qualify if:

  • Pregnant All female participants of child-bearing potential will have a pregnancy test performed prior to enrollment and will be counseled to use to two reliable methods of contraception for the duration of the trial.
  • \<18 years old
  • TB meningitis or tuberculoma at TB diagnosis
  • Rifampicin-resistant TB diagnosed by Xpert MTB/RIF test or a drug susceptibility test performed on a culture isolate.
  • On corticosteroids for another indication or on any other immunosuppressive medication within the past 7 days.
  • Uncontrolled diabetes mellitus
  • The following abnormal laboratory values:
  • Alanine aminotransferase \> 200 IU/l Absolute neutrophil count \< 500/mm3
  • Not on standard intensive phase TB treatment (Rifampicin, isoniazid, pyrazinamide and ethambutol)
  • Poor clinical response to TB treatment prior to ART as judged by the clinical investigators.
  • Hepatitis B surface antigen positive

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Site B Khayelitsha HIV/TB clinic

Cape Town, Western Cape, 7784, South Africa

Location

Related Publications (1)

  • Meintjes G, Stek C, Blumenthal L, Thienemann F, Schutz C, Buyze J, Ravinetto R, van Loen H, Nair A, Jackson A, Colebunders R, Maartens G, Wilkinson RJ, Lynen L; PredART Trial Team. Prednisone for the Prevention of Paradoxical Tuberculosis-Associated IRIS. N Engl J Med. 2018 Nov 15;379(20):1915-1925. doi: 10.1056/NEJMoa1800762.

    PMID: 30428290DERIVED

MeSH Terms

Conditions

Immune Reconstitution Inflammatory SyndromeTuberculosis

Interventions

Prednisone

Condition Hierarchy (Ancestors)

Immune System DiseasesMycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Intervention Hierarchy (Ancestors)

PregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Study Officials

  • Graeme Meintjes, MD MPH PhD

    University of Cape Town

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

August 12, 2013

First Posted

August 16, 2013

Study Start

August 30, 2013

Primary Completion

April 1, 2016

Study Completion

April 1, 2017

Last Updated

January 19, 2018

Record last verified: 2018-01

Locations

ZA(1)