NCT04271397

Brief Summary

Tuberculosis (TB) is the leading cause of death by infectious disease in the world, responsible for 1.6 million deaths in 2017. The treatment of active TB requires at least a 6-month combined antibiotic regimen and can cause heavy side effects. As a consequence, treatment adherence is not optimal, particularly in primary care settings. Rapid and reliable monitoring of anti-TB treatment adherence and efficacy is critical to provide adequate patient care and curb relapse episodes and acquired drug resistance. Investigators propose to evaluate the performance in terms of diagnosis accuracy and outcome prediction of four new biomarkers of active TB: 1) a double IGRA (Interferon Gamma Release Assay) including QuantiFERON-Gold Plus® and HBHA; 2) a whole blood transcriptomic analysis of mRNA (messenger Ribonucleic acid) expression of a panel of 150 genes; 3) a whole blood proteomic analysis; 4) an ex vivo immunophenotyping using flow and mass cytometry to characterize the lymphocyte populations.

Trial Health

77
On Track

Trial Health Score

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

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
6mo left

Started Sep 2019

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

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

Study Progress94%
Sep 2019Oct 2026

Study Start

First participant enrolled

September 30, 2019

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

December 23, 2019

Completed
2 months until next milestone

First Posted

Study publicly available on registry

February 17, 2020

Completed
6.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 10, 2026

Expected
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

October 10, 2026

Last Updated

August 12, 2024

Status Verified

August 1, 2024

Enrollment Period

7 years

First QC Date

December 23, 2019

Last Update Submit

August 9, 2024

Conditions

Outcome Measures

Primary Outcomes (1)

  • Concordance of the kinetics of biomarkers with the evolution of the disease

    It is a composite outcome. Evolution of the disease is defined by clinical status, radiological computed tomography evolution and negation of the mycobacterial culture of routine respiratory samples. The biomarkers assessed are: 1\) a combination of IGRAs test (QuantiFERON-Gold Plus and HBHA); 2) a transcriptomic signature; 3) a protein signature; 4) a phenotypic signature (by implementing an immunomonitoring approach).

    6 months

Secondary Outcomes (6)

  • Analytical characteristics of a combination of 2 IGRAs (QuantiFERON-TB Gold Plus (QFT-P) and HBHA) in the diagnosis / prognosis of tuberculosis disease.

    6 months

  • Performance of an immunomonitoring test by mass or flow cytometry in the diagnosis / prognosis of tuberculosis by measuring the dynamics of the blood population of T lymphocytes over time.

    6 months

  • Evaluate the performance of a test based on the interpretation of a transcriptomic signature in plasma in the diagnosis / prognosis of TB.

    6 months

  • Assess the performance of a test based on the interpretation of a protein signature in the diagnosis / prognosis of tuberculosis.

    6 months

  • Determine the achievement of target concentrations of rifampicin

    6 months

  • +1 more secondary outcomes

Study Arms (2)

Active tuberculosis

OTHER
Other: Multiple blood samples

Latent tuberculosis infection

OTHER
Other: Single blood sample

Interventions

Patients with active tuberculosis will have 5 research-specific blood samples: V1, (baseline) immediately before initiating anti-tuberculosis treatment, then 4 samples during anti-tuberculosis treatment and follow-up, i.e. at 48 hours (V2), 15 days (V3), 2 months (V4) and 6 months (V5) after initiation of treatment. The total volume of each sample will be 20 mL for a total of 100 mL.

Active tuberculosis

Patients with Latent tuberculosis infection will have a single specific sample of 14 mL.

Latent tuberculosis infection

Eligibility Criteria

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

You may qualify if:

  • Adult ≥ 18 year-old
  • Patients having given written consent
  • Patients accepting a follow up ≥ 6 months
  • Proven active tuberculosis (positive direct examination and/or PCR)
  • Latent tuberculosis infection assessed by positive IGRA

You may not qualify if:

  • Malignant solid tumor
  • Malignant hemopathy
  • Solid organ transplantation or hematopoietic stem cell transplantation
  • Immunosuppressive treatments (i.e. biologics, calcineurin inhibitors, corticosteroids)
  • Auto-inflammatory disease
  • Chronic liver diseases
  • Chronic infection with HIV, HCV (hepatitis C virus) or HBV (hepatitis B virus)
  • Antimycobacterial treatment initiated \> 7 days
  • Pregnancy or breastfeeding
  • Refusal to participate to the study
  • Persons deprived of their liberty by judicial or administrative decision
  • Protected adults
  • Patients not affiliated to health-care social security
  • The homeless

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Service des Maladies Infectieuses - Hôpital de la Croix Rousse - Hospices Civils de Lyon

Lyon, 69004, France

RECRUITING

Related Publications (1)

  • Bahuaud O, Genestet C, Hoffmann J, Dumitrescu O, Ader F. Opti-4TB: A protocol for a prospective cohort study evaluating the performance of new biomarkers for active tuberculosis outcome prediction. Front Med (Lausanne). 2022 Sep 14;9:998972. doi: 10.3389/fmed.2022.998972. eCollection 2022.

MeSH Terms

Conditions

TuberculosisLatent Tuberculosis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsLatent Infection

Intervention Hierarchy (Ancestors)

Specimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, OperativeInvestigative Techniques

Central Study Contacts

Florence ADER, M.D., Ph.D

CONTACT

Oana DUMITRESCU, M.D., PhD

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 23, 2019

First Posted

February 17, 2020

Study Start

September 30, 2019

Primary Completion (Estimated)

September 10, 2026

Study Completion (Estimated)

October 10, 2026

Last Updated

August 12, 2024

Record last verified: 2024-08

Data Sharing

IPD Sharing
Will not share

Locations