Nontuberculous Mycobacterial Pulmonary InfectionNCT05676138
PK and PD of Antibiotics for Treatment of Mycobacterium Abscessus Pulmonary Disease
An observational study of Nontuberculous Mycobacterial Pulmonary Infection, run by Seoul National University Hospital.
Trial summary
Investigating the PK and PD indices in patients with M. abscessus complex-PD who will be treated with a currently recommended regimen, minimum inhibitory concentrations of organism, and their relation with clinical outcomes Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Nontuberculous Mycobacterial Pulmonary Infection
- What is being tested?
- Measuring PK and PD indices in patients who receive conventional treatment
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2023to 31 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- Adult, Older adult
Study population: Patients with M. abscessus pulmonary disease, who receive conventional antibiotic treatment based on the currently recommended guideline.
Who may be able to join
- Age 20 years old or more
- Fulfilling the criteria of NTM-PD (1, 13), for which causative organism belongs to M. abscessus or M. massiliense
- Needing a new antibiotic treatment for M. abscessus complex-PD due to symptomatic aggravation, radiographic progression or both (those who have previous history of treatment are eligible)
- Consenting to receive antibiotic treatment based on currently recommended regimens (1, 13) and to participate in this study
Who cannot join
- Receiving any treatment for NTM-PD within 4 weeks
- Having end-stage renal disease needing hemodialysis, chronic liver disease, or active malignancy needing treatment during the treatment period
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Pharmacokinetics and Pharmacodynamics of Multidrug-regimens for Mycobacterium Abscessus Pulmonary Disease
Investigating the PK and PD indices in patients with M. abscessus complex-PD who will be treated with a currently recommended regimen, minimum inhibitory concentrations of organism, and their relation with clinical outcomes
Read the detailed description
Nontuberculous mycobacteria (NTM), consisting of more than 200 mycobacteria other than M. tuberculosis and M. leprae, is an environmental organism, which can be isolated from soil, dust and water. NTM can cause chronic diseases in human and the most common manifestation is pulmonary disease (PD) . During the last decades, the burden of NTM-PD in rapidly increasing in global. In South Korea, the incidence has increased from 1.0 per 100,000 population in 2003 to 17.9 per 100,00 population in 2016.
- abscessus complex is a group of rapidly growing mycobacteria (RGM). M. abscessus complex can be divided into three subspecies: M. abscessus subspecies abscessus (hereafter, referred to as M. abscessus), M. abscessus subspecies massiliense (M. massiliense), and M. abscessus subspecies bolletii (M. bolletii). Among the RGMs, M. abscessus complex is the most common pathogen for respiratory infection. With its distinctive surface properties and type VII secretion system (ESX-4), M. abscessus complex can cause progressive infection in patients with structural lung diseases such as cystic fibrosis.
Treatment of M. abscessus complex is extremely difficult. M. abscessus complex is generally resistant to most classes of antibiotics due to decreased cell wall permeability, induction of efflux pumps, and modification of drug targets. Especially, the presence of function erm(41) gene in M. abscessus confers inducible resistance to macrolide, which is the core drug of NTM-PD. As a result, multidrug regimens including at least three or four active drugs based on in vitro susceptibility are recommended for M. abscessus complex-PD.
Even though these complex and intensified treatments are administered in real clinical practice, the optimal drugs, dosage and duration of therapy are still not understood. Moreover, treatment outcomes are still unsatisfactory. According to the dataset from 303 patients with M. abscessus complex-PD, the treatment success rates were 33.0% for M. abscessus and 56.7% for M. massiliense, respectively. The unfavorable outcomes of currently recommended regimens are partly explained by an incomplete understanding of the relationship between pharmacokinetics (PK) of drugs used, in vitro susceptibility and treatment outcomes. To improve treatment outcomes, it should be preceded to figure out the potential efficacy of currently recommended regimens for M. abscessus complex-PD.
This will be performed as a prospective pharmacokinetic study for patients with M. abscessus complex-PD. Patients, who are scheduled to initiate treatment for M. abscessus complex-PD between 1 January 2023 and 31 December 2024 at Seoul National University Hospital, will be the subject of study. The size of population is estimated to be 40.
- Being tested
- Measuring PK and PD indices in patients who receive conventional treatment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Measuring PK and PD indices in patients who receive conventional treatmentOther
Measuring plasma concentration of commonly used antibiotics in NTM-PD
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak concentration (Cmax)
Cmax of guideline-recommended antibiotics in patients will be measured
Measured: 2 weeks of treatment
Time to Cmax
Time to Cmax of guideline-recommended antibiotics in patients will be measured
Measured: 2 weeks of treatment
Area under the curve from 0 to 24 hours after dosing
AUC24 of guideline-recommended antibiotics in patients will be measured
Measured: 2 weeks of treatment
Plasma half-life
Plasma half-life of guideline-recommended antibiotics in patients will be measured
Measured: 2 weeks of treatment
Secondary outcomes (2)
Time to culture positivity (days) by AUC24 (mg x h/L)
Time to culture positivity (mycobacterial culture in liquid media) from sputum represents the effect of treatment. The time to culture positivity (days) from sputum collected at 2 weeks of treatment will be measrued according to AUC24.
Measured: 2 weeks of treatment
Time to culture positivity (days) by Cmax (mg /L)
Time to culture positivity (mycobacterial culture in liquid media) from sputum represents the effect of treatment. The time to culture positivity (days) from sputum collected at 2 weeks of treatment will be measrued according to Cmax.
Measured: 2 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2023
- Study start1 Jan 2023 (estimated)
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nontuberculous Mycobacterial Pulmonary InfectionStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jae-Joon Yim, Seoul National University Hospital
- Investigators
- Jae-Joon Yim, MD, Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05676138
- Sponsor's protocol ID
- 2017-2154
- Status last verified
- Dec 2022
- First submitted
- 8 Dec 2022
- Last updated
- 9 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Pharmacodynamics of Multidrug-regimens for Mycobacterium Abscessus Pulmonary Disease
- ClinicalTrials.gov ID
- NCT05676138
- Acronym / sponsor ID
- 2017-2154
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- 1 Jan 2023 (estimated)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 9 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigating the PK and PD indices in patients with M. abscessus complex-PD who will be treated with a currently recommended regimen, minimum inhibitory concentrations of organism, and their relation with clinical outcomes
Detailed description
Nontuberculous mycobacteria (NTM), consisting of more than 200 mycobacteria other than M. tuberculosis and M. leprae, is an environmental organism, which can be isolated from soil, dust and water. NTM can cause chronic diseases in human and the most common manifestation is pulmonary disease (PD) . During the last decades, the burden of NTM-PD in rapidly increasing in global. In South Korea, the incidence has increased from 1.0 per 100,000 population in 2003 to 17.9 per 100,00 population in 2016.
- abscessus complex is a group of rapidly growing mycobacteria (RGM). M. abscessus complex can be divided into three subspecies: M. abscessus subspecies abscessus (hereafter, referred to as M. abscessus), M. abscessus subspecies massiliense (M. massiliense), and M. abscessus subspecies bolletii (M. bolletii). Among the RGMs, M. abscessus complex is the most common pathogen for respiratory infection. With its distinctive surface properties and type VII secretion system (ESX-4), M. abscessus complex can cause progressive infection in patients with structural lung diseases such as cystic fibrosis.
Treatment of M. abscessus complex is extremely difficult. M. abscessus complex is generally resistant to most classes of antibiotics due to decreased cell wall permeability, induction of efflux pumps, and modification of drug targets. Especially, the presence of function erm(41) gene in M. abscessus confers inducible resistance to macrolide, which is the core drug of NTM-PD. As a result, multidrug regimens including at least three or four active drugs based on in vitro susceptibility are recommended for M. abscessus complex-PD.
Even though these complex and intensified treatments are administered in real clinical practice, the optimal drugs, dosage and duration of therapy are still not understood. Moreover, treatment outcomes are still unsatisfactory. According to the dataset from 303 patients with M. abscessus complex-PD, the treatment success rates were 33.0% for M. abscessus and 56.7% for M. massiliense, respectively. The unfavorable outcomes of currently recommended regimens are partly explained by an incomplete understanding of the relationship between pharmacokinetics (PK) of drugs used, in vitro susceptibility and treatment outcomes. To improve treatment outcomes, it should be preceded to figure out the potential efficacy of currently recommended regimens for M. abscessus complex-PD.
This will be performed as a prospective pharmacokinetic study for patients with M. abscessus complex-PD. Patients, who are scheduled to initiate treatment for M. abscessus complex-PD between 1 January 2023 and 31 December 2024 at Seoul National University Hospital, will be the subject of study. The size of population is estimated to be 40.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patients with M. abscessus pulmonary disease, who receive conventional antibiotic treatment based on the currently recommended guideline.
Key inclusion criteria (4 listed)
- Age 20 years old or more
- Fulfilling the criteria of NTM-PD (1, 13), for which causative organism belongs to M. abscessus or M. massiliense
- Needing a new antibiotic treatment for M. abscessus complex-PD due to symptomatic aggravation, radiographic progression or both (those who have previous history of treatment are eligible)
- Consenting to receive antibiotic treatment based on currently recommended regimens (1, 13) and to participate in this study
Key exclusion criteria (2 listed)
- Receiving any treatment for NTM-PD within 4 weeks
- Having end-stage renal disease needing hemodialysis, chronic liver disease, or active malignancy needing treatment during the treatment period
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Measuring PK and PD indices in patients who receive conventional treatmentMeasuring plasma concentration of commonly used antibiotics in NTM-PD | Other | – |
Primary outcome
Peak concentration (Cmax)
Time frame: 2 weeks of treatment
Cmax of guideline-recommended antibiotics in patients will be measured
Time to Cmax
Time frame: 2 weeks of treatment
Time to Cmax of guideline-recommended antibiotics in patients will be measured
Area under the curve from 0 to 24 hours after dosing
Time frame: 2 weeks of treatment
AUC24 of guideline-recommended antibiotics in patients will be measured
Plasma half-life
Time frame: 2 weeks of treatment
Plasma half-life of guideline-recommended antibiotics in patients will be measured
2 secondary outcomes
Time to culture positivity (days) by AUC24 (mg x h/L)
Time frame: 2 weeks of treatment
Time to culture positivity (days) by Cmax (mg /L)
Time frame: 2 weeks of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jae-Joon Yim, MD principal investigator
Seoul National University Hospital
Questions about this trial
What is this clinical trial studying?
An observational study of Nontuberculous Mycobacterial Pulmonary Infection, run by Seoul National University Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nakwon Kwak, MD (82-2072-0616, n.kwak@snu.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak concentration (Cmax) (time frame: 2 weeks of treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2023.