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Systematic Empirical vs. Test-guided Anti-TB Treatment Impact in Severely Immunosuppressed HIV-infected Adults Initiating ART With CD4 Cell Counts <100/mm3

Information source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV-1 Infection

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

Phase: Phase 4

Status: Recruiting

Sponsored by: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Official(s) and/or principal investigator(s):
François-Xavier Blanc, MD, PhD, Principal Investigator, Affiliation: Université de Nantes, Institut du thorax, CHU Nantes, France
Kouao Médard Serge Domoua, MD, Principal Investigator, Affiliation: Service de Pneumologie, CHU de Treichville, Abidjan, Côte d'Ivoire

Overall contact:
François-Xavier Blanc, MD, PhD, Phone: +33 240 165 545, Email: xavier.blanc@chu-nantes.fr

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.

Clinical Details

Official title: Systematic Empirical vs. Test-guided Anti-tuberculosis Treatment Impact in Severely Immunosuppressed HIV-infected Adults Initiating Antiretroviral Therapy With CD4 Cell Counts <100/mm3: the STATIS Randomized Controlled Trial

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Primary outcome: All-cause mortality and incidence of invasive bacterial infections

Secondary outcome:

Incidence of confirmed/probable/possible TB

Incidence of grade 3 or 4 adverse events

Detailed description: Settings: Cambodia, Côte d'Ivoire, Uganda, Vietnam. Design: Multicentre, two-arm, unblinded randomized controlled superiority trial. Objective: To compare the 24-week risk of death and occurrence of invasive bacterial infection between two experimental strategies in HIV-1 infected adults who start ART with a CD4 count <100/mm3: (i) continuous extensive TB screening during follow-up each time the patient present with symptoms, versus (ii) systematic empirical TB treatment started 2 weeks before ART initiation. Trial strategies: At inclusion, participants will be randomized 1: 1 in two strategies of TB testing and treatment: extensive TB screening, or systematic empirical TB treatment. Extensive TB screening (arm 1): In this arm:

- TB screening point-of-care tests (Xpert MTB/RIF®, urine LAM) and chest X-ray will be

used extensively at randomisation (in all patients) and during follow-up (in patients with signs or symptoms suggestive of TB);

- Only patients who meet standardized criteria for TB at inclusion or during follow-up

will receive a standard TB treatment (2ERHZ/4RH);

- ART (tenofovir(TDF)-lamivudine (3TC)/emtricitabine(FTC) or zidovudine (AZT)-lamivudine+

efavirenz) will be started immediately after randomization in patients not put on TB treatment, and 2 weeks after initiation of TB treatment in others. Systematic empirical TB treatment (arm 2): In this arm:

- TB screening point-of-care tests will not be used;

- All patients will start a 6-month standard TB treatment (2ERHZ/4RH) at randomization;

ART (tenofovir-lamivudine/emtricitabine or zidovudine-lamivudine+ efavirenz) will be started 2 weeks after TB treatment initiation. Both strategies will apply to the first 24 weeks in the trial (intervention period). From week-24 to week-48, the choice of TB tests and the prescription of TB treatment will be left upon the decision of the investigator in both trial arms. Inclusion time: 24 months. Follow-up: each patient will be followed 48 weeks. Statistical analysis: the primary analysis will be intention to treat. It will compare the 24-week probability of death or invasive bacterial infection between arms. Sample size: 1050 participants. This will allow demonstration of a 40% reduction in the 24-week probability of death or invasive bacterial infection in arm 2, compared to arm 1 (α 5%; 1-β 80%).

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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.

Locations and Contacts

François-Xavier Blanc, MD, PhD, Phone: +33 240 165 545, Email: xavier.blanc@chu-nantes.fr

Sihanouk Hospital Center of Hope, Phnom Penh 2318, Cambodia; Recruiting
Laurence Borand, PharmD, PhD, Phone: +85 512 3 336 71, Email: lborand@pasteur-kh.org
Didier Laureillard, MD, Principal Investigator

ISS ImmunoSuppression Service, Mbarara 1956, Uganda; Recruiting
Conrad MUZOORA, MD, Phone: +256 772 547 175, Email: conradmuzoora@yahoo.com
Maryline Bonnet, MD, PhD, Principal Investigator

Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam; Recruiting
Didier Laureillard, MD, Phone: +84 169 7 061 034, Email: didier.laureillard@yahoo.fr
Didier Laureillard, MD, Principal Investigator

CePReF Centre de Prise en charge de Recherche et de Formation, Abidjan, Yopougon 1954, Côte D'Ivoire; Recruiting
Eugene Messou, MD PhD, Phone: +225 21 75 59 60, Email: messou_eugene@yahoo.fr
Christine Danel, MD, PhD, Principal Investigator

Additional Information

Starting date: September 2014
Last updated: March 31, 2015

Page last updated: August 23, 2015

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