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 TBIncidence 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
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