What side effects are associated with this type of intervention?

Common treatments for Tuberculosis include isoniazid, rifampin, ethambutol, and pyrazinamide. Isoniazid can cause liver toxicity and peripheral neuropathy. Rifampin is associated with liver toxicity, gastrointestinal disturbances, and can cause a red-orange discoloration of bodily fluids. Ethambutol may lead to optic neuritis, which can affect vision. Pyrazinamide can cause liver toxicity and hyperuricemia, which may lead to gout. These side effects highlight the importance of monitoring and optimizing treatment regimens to minimize toxicity while effectively treating TB.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Tuberculosis, including isoniazid, rifampin, ethambutol, and pyrazinamide. These drugs are often used in combination to effectively treat TB while minimizing the risk of drug resistance. The Optimized Treatment Regimens trial aims to enhance health outcomes and minimize toxicity, which aligns with the use of these established drugs in combination therapy to reduce side effects and improve patient outcomes. Newer treatment regimens and drugs are continually being studied to further optimize TB treatment, focusing on reducing treatment duration and adverse effects.

What other types of research exist?

Promising novel alternatives for tuberculosis treatment in 2024 include the use of new drug regimens such as BPaL (bedaquiline, pretomanid, and linezolid) for drug-resistant TB, which has shown high efficacy and reduced treatment duration. Additionally, the development of shorter, all-oral regimens for drug-sensitive TB, incorporating drugs like rifapentine and moxifloxacin, aims to improve adherence and reduce toxicity. Advances in host-directed therapies and the use of biomarkers to tailor treatment regimens also hold potential for optimizing outcomes and minimizing side effects.

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Antibiotic

Optimal Drug Regimen for Lung Disease (FORMaT Trial)

Phase 2 & 3

Recruiting

Research Sponsored by The University of Queensland

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects with respiratory cultures positive for M. abscessus (MABS) (sub species abscessus, sub species bolletii, or subspecies massiliense) are required to meet all 3 American Thoracic Society criteria (clinical, radiological and microbiological) for MABS pulmonary disease (PD)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12 months post trial completion

Awards & highlights

Summary

This trial tests different medicine combinations to find the best way to treat a tough lung infection in children and adults. The goal is to find the safest and most effective treatment.

Who is the study for?

This trial is for people with a lung condition caused by Mycobacterium abscessus, who meet specific clinical, radiological, and microbiological criteria. It's open to those with mixed infections if needed for treatment. Participants must be able to follow the trial plan and visit schedule. Those treated for MABS in the last year (except certain cases), pregnant or breastfeeding individuals, or anyone allergic to the drugs tested cannot join.

What is being tested?

The FORMaT trial is testing a combination of antibiotics including Cefoxitin, Linezolid, Bedaquiline and others against MABS pulmonary disease. The goal is to find the best treatment regimen that maximizes health outcomes while minimizing toxicity and burden on patients.

What are the potential side effects?

Potential side effects from these antibiotics may include allergic reactions, gastrointestinal issues like nausea or diarrhea, changes in blood counts leading to anemia or increased infection risk, liver toxicity, nerve damage causing numbness or pain, and possibly hearing loss due to Amikacin.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been diagnosed with M. abscessus lung disease based on clinical, radiological, and microbiological criteria.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12 months post trial completion

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12 months post trial completion

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12 months post trial completion for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Appendix A1 - MABS clearance from respiratory samples with tolerance at final outcome

Nested Study 1.3 Consolidation Therapy - Comparison of MABS clearance between those allocated to consolidation therapy with oral treatment and those allocated to consolidation with oral therapy and additional inhaled amikacin

Nested Study A1.1 Short Intensive Therapy - MABS Clearance

+3 more

Secondary outcome measures

Change in % Air Trapping scored using PRAGMA in chest CTs between Day 0 (screening) and at 12 weeks and at final outcome and between those who clear and those who do not clear MABS

Change in % Bronchiectasis scored using PRAGMA in chest CTs between Day 0 (screening) and at 12 weeks and at final outcome and between those who clear and those who do not clear MABS

Change in % Disease scored using PRAGMA in chest CTs between Day 0 (screening) and at 12 weeks and at final outcome and between those who clear and those who do not clear MABS

+9 more

Other outcome measures

Examine the MABS clearance status at twelve (12 months) after time point final

Side effects data

From 2018 Phase 4 trial • 190238 Patients • NCT02047981

Death

100%

80%

60%

40%

20%

Study treatment Arm

Biannual Mass Oral Azithromycin

Biannual Mass Oral Placebo

Trial Design

5Treatment groups

Experimental Treatment

Active Control

Group I: Intensive Therapy CExperimental Treatment7 Interventions

Following Randomisation 1, Participants will receive intensive drug therapy in the form of IV amikacin, IV tigecycline, IV cefoxitin/imipenem + oral azithromycin/oral clarithromycin.

Group II: Intensive Therapy BExperimental Treatment8 Interventions

Following Randomisation 1, Participants will receive inhaled amikacin (IA), IV tigecycline, IV cefoxitin/imipenem + oral azithromycin/oral clarithromycin AND clofazimine.

Group III: Consolidation BExperimental Treatment11 Interventions

Inhaled amikacin (IA), oral clofazimine + oral azithromycin/oral clarithromycin in combination with one to three of the following oral antibiotics: oral linezolid, oral co-trimoxazole, oral doxycycline, oral moxifloxacin, oral bedaquiline (adults only), oral rifabutin.

Group IV: Consolidation AActive Control10 Interventions

Oral clofazimine + oral azithromycin/oral clarithromycin in combination with one to three of the following oral antibiotics: oral linezolid, oral co-trimoxazole, oral doxycycline, oral moxifloxacin, oral bedaquiline (adults only), oral rifabutin.

Group V: Intensive Therapy AActive Control8 Interventions

Following Randomisation 1, Participants will receive intensive drug therapy in the form of IV amikacin, IV tigecycline, IV cefoxitin/imipenem + oral azithromycin AND clofazimine.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Amikacin

2016

Completed Phase 4

~540

Bedaquiline

2020

Completed Phase 3

~3900

Tigecycline

2008

Completed Phase 4

~2270

Imipenem

2018

Completed Phase 4

~830

Azithromycin

2018

Completed Phase 4

~274950

Clarithromycin

2017

Completed Phase 4

~3950

Clofazimine

2022

Completed Phase 4

~2900

Ethambutol

2023

Completed Phase 4

~3090

Linezolid

2002

Completed Phase 4

~3890

co-trimoxazole

2013

Completed Phase 2

~20

Rifabutin

2003

Completed Phase 4

~890

Doxycycline

2008

Completed Phase 4

~2430

Moxifloxacin

2013

Completed Phase 4

~3290

0 / 1Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for tuberculosis (TB) include isoniazid, rifampin, ethambutol, and pyrazinamide. Isoniazid inhibits the synthesis of mycolic acids, essential components of the mycobacterial cell wall. Rifampin targets bacterial RNA polymerase, thereby inhibiting RNA synthesis. Ethambutol interferes with the synthesis of the mycobacterial cell wall by inhibiting arabinosyl transferases. Pyrazinamide disrupts mycobacterial cell membrane metabolism and transport functions. Understanding these mechanisms is crucial for TB patients as it helps in designing optimized treatment regimens that maximize efficacy while minimizing toxicity, thereby improving health outcomes and reducing the burden of side effects.

Adult systemic anaplastic large-cell lymphoma: recommendations for diagnosis and management.Impact of patient characteristics and infection type on clinical outcomes of patients who received linezolid or vancomycin for complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus: a pooled data analysis.Virological treatment failure of protease inhibitor therapy in an unselected cohort of HIV-infected patients.