NCT02057796

Brief Summary

In countries with a high tuberculosis (TB) prevalence, TB and invasive bacterial infections are leading causes of early death in patients who initiate antiretroviral therapy (ART) with advanced immunodeficiency. We hypothesize that a systematic 6-month empirical TB treatment initiated 2 weeks before the introduction of ART in HIV-infected adults with severe immunosuppression (CD4\<100/mm3) and no overt evidence of TB will reduce the risk of death and invasive bacterial infections. This strategy will be compared to one of extensive TB testing using point-of-care tests (Xpert MTB/RIF® and urine lipoarabinomanan LAM) and chest X-ray to identify and treat only patients with at least one positive test suggestive of TB.

Trial Health

90
On Track

Trial Health Score

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

Enrollment
1,050

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Sep 2014

Longer than P75 for phase_4

Geographic Reach
4 countries

4 active sites

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

February 5, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 7, 2014

Completed
7 months until next milestone

Study Start

First participant enrolled

September 1, 2014

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2018

Completed
Last Updated

October 19, 2020

Status Verified

October 1, 2020

Enrollment Period

3.6 years

First QC Date

February 5, 2014

Last Update Submit

October 13, 2020

Conditions

HIV-1 Infection

Keywords

HIV-1TuberculosisSystematic empiric TB treatmentARTTB diagnosisXpert MTB/RIF®Urine LAM

Outcome Measures

Primary Outcomes (1)

  • All-cause mortality and incidence of invasive bacterial infections

    The primary endpoint is the composite of (i) 24-week all-cause mortality and (ii) 24-week incidence of invasive bacterial infections

    24 weeks

Secondary Outcomes (2)

  • Incidence of confirmed/probable/possible TB

    24 Weeks and 48 weeks

  • Incidence of grade 3 or 4 adverse events

    24 Weeks and 48 weeks

Other Outcomes (2)

  • Incidence of TB-associated IRIS

    24 Weeks and 48 Weeks

  • Incidence of AIDS-defining diseases other than TB

    24 Weeks and 48 Weeks

Study Arms (2)

Xpert MTB/RIF®, Determine TB LAM, Chest X-ray

EXPERIMENTAL

Arm1 Extensive TB screening: In this arm, point-of-care tests for TB will be used at randomization (in all patients) and at each scheduled or unscheduled follow-up visit (in patients with signs or symptoms suggestive of TB and no clear alternative diagnosis); TB treatment will only be prescribed to patients with a diagnosis of TB

Device: Xpert MTB/RIF®, Determine TB LAM, Chest X-rayDrug: ART (Atripla, Truvada, Efavirenz, Combivir)Drug: Rifampin, isoniazid, pyrazinamide, ethambutol

Rifampin, isoniazid, pyrazinamide, ethambutol

EXPERIMENTAL

Arm 2: Systematic Empiric treatment (Rifampicin,isoniazid, pyrazinamide, ethambutol) ART In this arm, all patients will start a systematic 6-month TB treatment at randomization. TB screening tests will not systematically be used neither at randomization nor while patients are on TB treatment.

Drug: ART (Atripla, Truvada, Efavirenz, Combivir)Drug: Rifampin, isoniazid, pyrazinamide, ethambutol

Interventions

Xpert MTB/RIF®, Determine TB LAM, Chest X-rayDEVICE

The following point-of-care TB tests will be systematically performed: Xpert MTB/RIF® on sputum (in all patients able to provide sputum; no sputum induction will be requested in others), Urine LAM (all patients). Depending on clinical presentation, Xpert MTB/RIF® will also be performed on any relevant extra-pulmonary specimen. TB treatment will depend on the result of the tests: Criteria met for confirmed or probable TB : TB treatment will be initiated immediately (Visit 1) followed by ART initiation 2 weeks later (Visit 2); No evidence of confirmed or probable TB: ART will be started immediately (Visit 1).

Xpert MTB/RIF®, Determine TB LAM, Chest X-ray
ART (Atripla, Truvada, Efavirenz, Combivir)DRUG

* ART (TDF-3TC/FTC or AZT-3TC + efavirenz) will be started immediately after randomization in patients not put on TB treatment, and 2 weeks after initiation of TB treatment in others. * ART will be initiated 2 weeks after the onset of TB treatment (V2) for Arm 2

Also known as: ART
Rifampin, isoniazid, pyrazinamide, ethambutolXpert MTB/RIF®, Determine TB LAM, Chest X-ray
Rifampin, isoniazid, pyrazinamide, ethambutolDRUG

Arm 1: Only patients who meet standardized criteria for TB at inclusion or during follow-up will receive a standard TB treatment (2ERHZ/4RH); Arm 2: • All patients will start a 6-month standard TB treatment (2ERHZ/4RH) at randomization

Also known as: Systematic Empiric treatment
Rifampin, isoniazid, pyrazinamide, ethambutolXpert MTB/RIF®, Determine TB LAM, Chest X-ray

Eligibility Criteria

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

You may qualify if:

  • Age ≥18 years;
  • HIV-1 infection as documented at any time prior to trial entry, as per national testing procedures;
  • CD4 \<100 cells/mm3;
  • No history of antiretroviral drug use (except transient ART for PMTCT);
  • Able to correctly understand the trial and to sign the informed consent.

You may not qualify if:

  • HIV-2 co-infection;
  • Contra-indication to efavirenz;
  • Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \>5 times the upper limit of normal;
  • Creatinine clearance \<50 ml/min;
  • Overt evidence that TB treatment should be started immediately;
  • History of TB treatment in the past 5 years;
  • Ongoing TB chemoprophylaxis (isoniazid preventive therapy);
  • Any condition that would lead to differ ART initiation (e.g. acute condition requiring investigations and/or treatment prior to ART initiation);
  • Current pregnancy or breastfeeding.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Sihanouk Hospital Center of Hope

Phnom Penh, 2318, Cambodia

Location

CePReF Centre de Prise en charge de Recherche et de Formation

Abidjan, Yopougon, 1954, Côte d’Ivoire

Location

ISS ImmunoSuppression Service

Mbarara, 1956, Uganda

Location

Pham Ngoc Thach Hospital

Ho Chi Minh City, Vietnam

Location

Related Publications (2)

  • Bonnet M, Gabillard D, Domoua S, Muzoora C, Messou E, Sovannarith S, Nguyen DB, Badje A, Juchet S, Bunnet D, Borand L, Natukunda N, Tran TH, Anglaret X, Laureillard D, Blanc FX; Systematic empirical vs. Test-guided Anti-tuberculosis Treatment Impact in Severely immunosuppressed HIV-infected adults initiating antiretroviral therapy with CD4 cell counts <100/mm3 (STATIS) Agence Nationale de Recherche sur le Sida et les hepatites virales (ANRS) 12290 Trial Team. High Performance of Systematic Combined Urine Liboarabinomannan Test and Sputum Xpert MTB/RIF for Tuberculosis Screening in Severely Immunosuppressed Ambulatory Adults With Human Immunodeficiency Virus. Clin Infect Dis. 2023 Jul 5;77(1):112-119. doi: 10.1093/cid/ciad125.

    PMID: 36883573DERIVED

  • Blanc FX, Badje AD, Bonnet M, Gabillard D, Messou E, Muzoora C, Samreth S, Nguyen BD, Borand L, Domergue A, Rapoud D, Natukunda N, Thai S, Juchet S, Eholie SP, Lawn SD, Domoua SK, Anglaret X, Laureillard D; STATIS ANRS 12290 Trial Team. Systematic or Test-Guided Treatment for Tuberculosis in HIV-Infected Adults. N Engl J Med. 2020 Jun 18;382(25):2397-2410. doi: 10.1056/NEJMoa1910708.

    PMID: 32558469DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

Diagnostic ImagingEfavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug CombinationEmtricitabine, Tenofovir Disoproxil Fumarate Drug Combinationefavirenzlamivudine, zidovudine drug combinationRifampinIsoniazidPyrazinamideEthambutol

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Intervention Hierarchy (Ancestors)

Diagnostic Techniques and ProceduresDiagnosisTenofovirOrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsOxazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsEmtricitabineDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesAdeninePurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingDrug CombinationsPharmaceutical PreparationsDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesRifamycinsHeterocyclic Compounds, 4 or More RingsLactams, MacrocyclicMacrocyclic CompoundsPolycyclic CompoundsHydrazinesIsonicotinic AcidsAcids, HeterocyclicPyridinesPyrazinesEthylenediaminesDiaminesPolyaminesAmines

Study Officials

  • François-Xavier Blanc, MD, PhD

    Université de Nantes, Institut du thorax, CHU Nantes, France

    PRINCIPAL INVESTIGATOR

  • Kouao Médard Serge Domoua, MD

    Service de Pneumologie, CHU de Treichville, Abidjan, Côte d'Ivoire

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 5, 2014

First Posted

February 7, 2014

Study Start

September 1, 2014

Primary Completion

April 1, 2018

Study Completion

April 1, 2018

Last Updated

October 19, 2020

Record last verified: 2020-10

Locations

UG(1)VN(1)CÔ(1)CA(1)