Ongoing Clinical Trials for Pulmonary Tuberculosis
There are currently 6 clinical trials investigating new treatments and drug combinations for pulmonary tuberculosis across Europe. These studies focus on improving treatment outcomes for both drug-sensitive and drug-resistant forms of the disease, testing various medication combinations including novel antibiotics, host-directed therapies, and shorter treatment regimens aimed at reducing treatment duration and improving patient quality of life.
Clinical trial locations
- France
- Italy
- Romania
- Spain
Study of cysteamine combined with standard tuberculosis treatment in adults with pulmonary tuberculosis
This study is being conducted in Italy and explores a novel approach to treating pulmonary tuberculosis by combining standard therapy with cysteamine, also known as Cystagon. This represents a host-directed treatment strategy, meaning it works by enhancing the patient’s immune system response rather than directly attacking the bacteria.
Main inclusion criteria: Participants must be adults between 18 and 65 years old with newly diagnosed pulmonary tuberculosis confirmed by positive sputum tests and chest X-ray findings. They must weigh at least 50 kilograms and have a Karnofsky score of 60% or higher, indicating they can perform most daily activities. The tuberculosis bacteria must be sensitive to standard medications. Female participants must be surgically sterile or postmenopausal, and all participants must be willing to stay in hospital for 4 weeks and attend all follow-up appointments.
Main exclusion criteria: The study excludes pregnant or breastfeeding women, individuals with severe liver or kidney disease, those with drug-resistant tuberculosis, people with serious heart conditions or uncontrolled high blood pressure, and anyone with HIV infection or other serious immune system disorders. Participants with active substance abuse, severe mental health conditions affecting study compliance, or a history of allergic reactions to cysteamine are also excluded.
Study focus: The primary goal is to determine whether adding cysteamine to standard tuberculosis treatment is safe and well-tolerated. Researchers will monitor treatment response through blood, urine, and sputum samples collected at regular intervals during a 4-week hospital stay, with follow-up continuing for 6 months. The study aims to evaluate both the safety profile and the effectiveness of this combination therapy in fighting the infection.
Investigational drugs: Cysteamine (Cystagon 50 mg capsules) is the investigational medication being tested alongside standard tuberculosis therapy. Unlike traditional antibiotics that directly attack bacteria, cysteamine works by targeting the host’s immune system to potentially improve treatment effectiveness. Standard tuberculosis therapy consists of the established combination of antibiotics typically used to treat TB infections.
Study on the Effects of Tedizolid and Linezolid for Patients with Suspected Lung Tuberculosis
This French study evaluates two oxazolidinone antibiotics, tedizolid and linezolid, comparing their early effects against tuberculosis bacteria to standard treatment. The research focuses on how quickly these medications reduce bacterial load during the first days of treatment.
Main inclusion criteria: Participants must be between 18 and 74 years old with a first suspected lung tuberculosis infection confirmed by symptoms, abnormal chest imaging, and positive sputum tests showing tuberculosis without rifampicin resistance. Women of childbearing age must use effective birth control during the study and for 6 months afterward, and men must use contraception during treatment and for 3 months after. Participants must sign informed consent and either have social security coverage or have applied for state medical assistance.
Main exclusion criteria: The study excludes patients with previous tuberculosis infections, those outside the specified age range, and individuals considered part of vulnerable populations requiring special protection or care.
Study focus: The trial assesses the early bactericidal activity of tedizolid and linezolid by measuring how effectively they reduce bacteria in sputum samples during the first 7 days of treatment. Researchers will compare these results to standard quadruple therapy, monitoring bacterial reduction at multiple time points and evaluating medication concentrations in the body along with any toxicity or adverse effects.
Investigational drugs: Tedizolid (200 mg daily) and linezolid (1200 mg daily) are both oxazolidinone antibiotics that work by blocking bacterial protein synthesis, preventing bacteria from growing and multiplying. Both are administered orally and compared against standard tuberculosis therapy consisting of rifampicin, isoniazid, pyrazinamide, and ethambutol.
Study of bedaquiline, pretomanid, linezolid and moxifloxacin combination treatment for patients with multidrug-resistant tuberculosis in France
This French trial investigates a shortened 6-month treatment regimen for multidrug-resistant tuberculosis, a form of the disease that doesn’t respond to standard first-line medications. The study compares this new approach to conventional longer treatments used in France between 2006 and 2022.
Main inclusion criteria: Participants must be 18 years or older with laboratory-confirmed rifampicin-resistant tuberculosis. They must be able to provide informed consent and agree to use effective birth control (women during treatment and for 6 months after; men during treatment and for 3 months after, unless they’ve had a vasectomy). Valid health insurance coverage or eligibility for state medical aid is required.
Main exclusion criteria: The study excludes individuals under 18, those with known allergies to any study medications, pregnant or breastfeeding women, and people with severe liver problems, serious heart conditions, or severe kidney disease requiring dialysis. Also excluded are those with active substance abuse affecting treatment adherence, HIV infection with severely low CD4 counts (below 100 cells/mm³), mental health conditions preventing understanding of study procedures, recent treatment with study medications, or participation in another trial within 30 days.
Study focus: The primary objective is to determine if the 6-month BPaLM regimen (bedaquiline, pretomanid, linezolid, and moxifloxacin) works as effectively as conventional 18-24 month treatments. Success will be evaluated 18 months after starting treatment, with careful monitoring throughout for treatment interruptions and adherence.
Investigational drugs: BPaLM is a four-drug combination consisting of bedaquiline (400 mg daily), pretomanid (200 mg daily), linezolid (600 mg daily), and moxifloxacin (400 mg daily). Each component has a unique mechanism: bedaquiline inhibits bacterial ATP synthase, pretomanid causes cellular damage within bacteria, linezolid prevents bacterial protein synthesis, and moxifloxacin inhibits bacterial DNA replication. All medications are taken orally.
Study on the Safety and Effectiveness of CC-11050 and Metformin for Patients with Rifampin-Resistant Tuberculosis
This Romanian study explores whether adding host-directed therapies to standard tuberculosis treatment can improve outcomes in rifampin-resistant cases. The trial tests two medications with different mechanisms: CC-11050 (an anti-inflammatory) and metformin (commonly used for diabetes but potentially beneficial against infections).
Main inclusion criteria: Participants must be between 16 and 65 years old, weighing between 30 and 90 kilograms, with positive sputum tests confirming rifampin-resistant tuberculosis. Chest X-rays must show moderate or very advanced disease. HIV-negative individuals can participate from any site, while HIV-positive individuals can only enroll at African study sites if they have CD4 counts above 100/μl and are receiving or willing to start antiretroviral therapy. All sexually active participants must use effective birth control during treatment, and those aged 16-17 require parental consent.
Main exclusion criteria: The study excludes patients without multidrug-resistant pulmonary tuberculosis, those not resistant to rifampicin, individuals outside the specified age range, and members of vulnerable populations.
Study focus: The trial evaluates whether CC-11050 and metformin can help improve lung function recovery and eradicate tuberculosis infection when added to standard therapy. The primary endpoints, assessed at 6 months, include lung function improvement and stable culture conversion. Long-term follow-up continues for up to 18 months to evaluate durability of treatment effects.
Investigational drugs: CC-11050 is an immunomodulatory agent that reduces inflammation and enhances immune response. Metformin (Metformin Zentiva 500 mg) is being investigated for its potential antimicrobial properties, working by affecting cellular metabolism and enhancing immune response to help clear infection. Both are administered orally alongside standard tuberculosis treatment.
Study on Gremubamab for Patients with Bronchiectasis and Chronic Pseudomonas Aeruginosa Infection
This Spanish trial focuses on bronchiectasis complicated by chronic bacterial infection rather than tuberculosis itself, though bronchiectasis can be a consequence of tuberculosis. The study evaluates gremubamab, a monoclonal antibody treatment aimed at reducing bacterial burden in the lungs.
Main inclusion criteria: Participants must be between 18 and 85 years old with a clinical diagnosis of bronchiectasis confirmed by previous chest CT scan showing the condition in one or more lung areas. They must have had Pseudomonas aeruginosa detected in lung samples at least once in the 24 months before enrollment and provide a sputum sample testing positive for this bacteria at screening and within 35 days before randomization. All participants must be able to understand and sign informed consent.
Main exclusion criteria: The study excludes individuals without bronchiectasis and chronic Pseudomonas aeruginosa infection, those outside the specified age range, and members of vulnerable populations requiring special protection.
Study focus: The trial aims to determine if gremubamab can effectively reduce Pseudomonas aeruginosa bacteria in sputum over 12 weeks compared to placebo. Regular assessments occur on days 7, 14, 28, 56, 84, and 168 to monitor bacterial burden and other health indicators, with the primary endpoint evaluation on day 84.
Investigational drugs: Gremubamab is a monoclonal antibody administered intravenously that targets specific bacterial components to reduce bacterial presence in the lungs. It is designed to help patients with bronchiectasis better manage chronic bacterial infections that contribute to ongoing lung damage.
Study on the Effectiveness and Safety of High-Dose Rifampicin, Moxifloxacin, and Linezolid for Patients with Pulmonary Tuberculosis
This Spanish study investigates whether using higher doses of rifampicin combined with moxifloxacin and linezolid can more effectively treat drug-sensitive pulmonary tuberculosis compared to standard treatment regimens.
Main inclusion criteria: Participants must be over 18 years old with smear-positive pulmonary tuberculosis, meaning tuberculosis bacteria are visible in lung mucus samples under microscopy. They must sign informed consent after understanding study procedures. Women of childbearing age must have a negative pregnancy test unless they are infertile due to hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.
Main exclusion criteria: The study excludes patients without smear-positive pulmonary tuberculosis, those outside the specified age range, and individuals belonging to vulnerable populations needing special care or protection.
Study focus: The trial evaluates whether the combination of high-dose rifampicin, high-dose moxifloxacin, and linezolid can achieve sterilization of sputum culture by the end of 8 weeks more effectively than standard treatment. Researchers will closely monitor treatment efficacy, safety (particularly adverse events of grade 3 or higher), tolerability, and quality of life throughout the 8-week treatment period.
Investigational drugs: High-dose rifampicin works by inhibiting bacterial RNA synthesis to stop bacteria from multiplying. High-dose moxifloxacin, a fluoroquinolone antibiotic, inhibits bacterial DNA gyrase and topoisomerase IV enzymes crucial for bacterial DNA replication. Linezolid, an oxazolidinone antibiotic, prevents bacterial protein synthesis. All three medications are administered orally as tablets or capsules.
Summary
The 6 ongoing clinical trials for pulmonary tuberculosis demonstrate a diverse research landscape across Europe, with particular concentration in France and Spain, each hosting two trials. The studies reflect current priorities in tuberculosis research, including development of shorter treatment regimens for drug-resistant disease, evaluation of host-directed therapies that enhance immune response rather than directly targeting bacteria, and optimization of antibiotic combinations to improve treatment outcomes.
Notable trends include multiple studies investigating oxazolidinone antibiotics (tedizolid and linezolid) and fluoroquinolones (moxifloxacin), suggesting these drug classes are of significant interest for both drug-sensitive and drug-resistant tuberculosis. The BPaLM regimen trial represents a particularly important development, offering the possibility of reducing multidrug-resistant tuberculosis treatment from 18-24 months to just 6 months, which could significantly improve patient adherence and quality of life.
The geographic distribution shows Western European countries are leading tuberculosis clinical research, while Romania is conducting important work on rifampin-resistant disease with novel host-directed therapies including repurposed medications like metformin. These trials collectively aim to address the urgent need for more effective, shorter, and better-tolerated treatments for both standard and drug-resistant forms of pulmonary tuberculosis.
