Meningitis, TuberculousPhase 2NCT01158755
Intensified Treatment Regimens for TB Meningitis: PK, PD and Tolerability Study
A Phase 2 study testing Moxifloxacin in people with Meningitis, Tuberculous and Pharmacokinetics, run by Universitas Padjadjaran at 1 site in Indonesia.
Trial summary
Tuberculous meningitis (TBM) is the most lethal form of tuberculosis infection, and is diagnosed in approximately 5-10% of TB patients. The incidence of TBM has increased considerably during the last decade, partly due to the HIV epidemic. Without treatment, virtually all patients with TB meningitis will die. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Meningitis, Tuberculous, Pharmacokinetics, Pharmacodynamics
- What is being tested?
- Moxifloxacin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteIndonesia
- Study dates
- Oct 2010to Jun 2012
- Phase
- Phase 2
- 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 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Tuberculous meningitis, diagnosed based on clinical and/or CSF criteria
- Age 15 years old or more
- Hospitalized for the treatment
Who cannot join
- Pregnancy/lactation
- On TB treatment within 7 days before inclusion
- Elevated liver enzyme (> 5x than normal values)
- Known hypersensitivity/intolerance to rifampicin or moxifloxacin
- Prolonged QTc interval in ECG or other detectable cardiac arrythmias, in the absence of hypokalemia
- Refusal to be included in the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of Intensive Treatment Regimens and Standard Treatment Regimen for Tuberculous Meningitis: Pharmacokinetics, Pharmacodynamics and Tolerability Study
Tuberculous meningitis (TBM) is the most lethal form of tuberculosis infection, and is diagnosed in approximately 5-10% of TB patients. The incidence of TBM has increased considerably during the last decade, partly due to the HIV epidemic. Without treatment, virtually all patients with TB meningitis will die. With the current treatment regimens, TBM is fatal in approximately 30-50% of cases, and responsible for severe disability in a similar proportion of survivors.
Worldwide, Indonesia the third highest case load of tuberculosis with an estimated 500,000 new patients / year. Representative data are lacking, but it is clear that TBM is a growing problem. For instance, in Hasan Sadikin Hospital, the top-referral hospital for West Java Province (population 40 million), Indonesia, 40-50 cases of TBM were treated yearly in the late 90's compared to approximately 100 in recent years.
There is very little evidence for the current treatment regimen for TBM, which dates back to the late 60's. Therefore, there is an urgent need to evaluate intensified treatment of TBM in randomized trials. We hypothesize that higher dose rifampicin, moxifloxacin (possibly also at high dose), or both will improve outcome of TBM. To determine the experimental regimen(s) which should be compared with current regimen in phase 3 trials, we want to evaluate pharmacokinetic aspects and toxicity of candidate regimens in a phase 2 clinical trial in 60 patients with TBM in Indonesia.
- Being tested
- Moxifloxacin
- Keywords
- Meningitis, tuberculous, Intensified Regimen, PK/PD and tolerability, Outcome
- Medical subject headings
- Tuberculosis, Meningeal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MoxifloxacinDrug
Also called Avelox (r)
Subjects on both arms will further be randomized into receiving moxifloxacin either in standard dose (400 mg p.o.), high dose (800 mg p.o.) of moxifloxacin, or not receiving moxifloxacin (ethambutol 750 mg p.o., instead) Intervention drug will be given for 14 days, and the drug will be switched to ethambutol 750 mg p.o. (in accordance with National TB Program)
| Study group | Role | What they receive |
|---|---|---|
| Standard dose rifampisin | Active comparator | Subjects in this arm receive 450 mg rifampicin orally.
In accordance with national TB treatment standard that encourages the use of 4 drugs, all subjects -both in active comparator and experimental arm- will also receive isoniazide 300 mg p.o. and pyrazinamide 1500 mg p.o.
Unconscious subjects will receive oral drugs via nasogastric tubes (NGT) Receives: Drug: Moxifloxacin |
| High dose rifampisin | Experimental | Subjects in this arm receive 600 mg Rifampisin i.v. for 14 days, and the dosage will be switched to 450 mg Rifampisin p.o afterwards until completion of TB medication (in accordance with National TB Program)
In accordance with national TB treatment standard that encourages the use of 4 drugs, all subjects -both in active comparator and experimental arm- will also receive isoniazide 300 mg p.o. and pyrazinamide 1500 mg p.o.
Unconscious subjects will receive oral drugs via nasogastric tubes (NGT) Receives: Drug: Moxifloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rifampicin and Moxifloxacin concentration in plasma and CSF
On sampling day (one of the first 3 days of hospitalization), we will measure plasma and CSF drug concentration at several time points.
Plasma drug concentration will be measured at 6 time points (hour 0, 1, 2, 4, 6 and 12).
CSF drug concentration at 2 time points: (1) hour 3-6 post dose on the same blood sampling day and (2) within 5 days after the 1st day of TB drug administration, 1-3 hours after drug intake
Measured: Plasma drug concentration samplings at 0, 1, 2, 4, 6 and 24h post dose (6 time points). CSF samples at 2 time points.
Secondary outcomes (1)
Early and late mortality
We will measure early (within first month of TB treatment) and late (after 6 months of TB treatment) mortality
Measured: 1st and 6th month of TB treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2010 (estimated)
- Study startOct 2010
- Primary completionDec 2011
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Meningitis, TuberculousStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitas Padjadjaran
- Sponsor type
- University, hospital or other
- Collaborators
- Radboud University Medical Center
- Responsible party
- Principal investigator, Ahmad Rizal Ganiem, Universitas Padjadjaran
- Investigators
- Rovina Ruslami, PhD, Principal investigator, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01158755
- Sponsor's protocol ID
- TB-201006.01
- Status last verified
- Jun 2012
- First submitted
- 7 Jul 2010
- Last updated
- 7 Jun 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Te Brake L, Dian S, Ganiem AR, Ruesen C, Burger D, Donders R, Ruslami R, van Crevel R, Aarnoutse R. Pharmacokinetic/pharmacodynamic analysis of an intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis. Int J Antimicrob Agents. 2015 May;45(5):496-503. doi: 10.1016/j.ijantimicag.2014.12.027. Epub 2015 Feb 7.
PubMed 25703312Ruslami R, Ganiem AR, Dian S, Apriani L, Achmad TH, van der Ven AJ, Borm G, Aarnoutse RE, van Crevel R. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. Lancet Infect Dis. 2013 Jan;13(1):27-35. doi: 10.1016/S1473-3099(12)70264-5. Epub 2012 Oct 25.
PubMed 23103177
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Intensive Treatment Regimens and Standard Treatment Regimen for Tuberculous Meningitis: Pharmacokinetics, Pharmacodynamics and Tolerability Study
- ClinicalTrials.gov ID
- NCT01158755
- Acronym / sponsor ID
- TB-201006.01
- Keywords
- Meningitis, tuberculous, Intensified Regimen, PK/PD and tolerability, Outcome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Universitas PadjadjaranUniversity, hospital or other
- Collaborators
- Radboud University Medical Center
- Study start
- Oct 2010
- Primary completion
- Dec 2011 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 8 Jul 2010 (estimated)
- 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.
Tuberculous meningitis (TBM) is the most lethal form of tuberculosis infection, and is diagnosed in approximately 5-10% of TB patients. The incidence of TBM has increased considerably during the last decade, partly due to the HIV epidemic. Without treatment, virtually all patients with TB meningitis will die. With the current treatment regimens, TBM is fatal in approximately 30-50% of cases, and responsible for severe disability in a similar proportion of survivors.
Worldwide, Indonesia the third highest case load of tuberculosis with an estimated 500,000 new patients / year. Representative data are lacking, but it is clear that TBM is a growing problem. For instance, in Hasan Sadikin Hospital, the top-referral hospital for West Java Province (population 40 million), Indonesia, 40-50 cases of TBM were treated yearly in the late 90's compared to approximately 100 in recent years.
There is very little evidence for the current treatment regimen for TBM, which dates back to the late 60's. Therefore, there is an urgent need to evaluate intensified treatment of TBM in randomized trials. We hypothesize that higher dose rifampicin, moxifloxacin (possibly also at high dose), or both will improve outcome of TBM. To determine the experimental regimen(s) which should be compared with current regimen in phase 3 trials, we want to evaluate pharmacokinetic aspects and toxicity of candidate regimens in a phase 2 clinical trial in 60 patients with TBM in Indonesia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard dose rifampisin | Active comparator | Drug: MoxifloxacinSubjects in this arm receive 450 mg rifampicin orally. In accordance with national TB treatment standard that encourages the use of 4 drugs, all subjects -both in active comparator and experimental arm- will also receive isoniazide 300 mg p.o. and pyrazinamide 1500 mg p.o. Unconscious subjects will receive oral drugs via nasogastric tubes (NGT) |
| High dose rifampisin | Experimental | Drug: MoxifloxacinSubjects in this arm receive 600 mg Rifampisin i.v. for 14 days, and the dosage will be switched to 450 mg Rifampisin p.o afterwards until completion of TB medication (in accordance with National TB Program) In accordance with national TB treatment standard that encourages the use of 4 drugs, all subjects -both in active comparator and experimental arm- will also receive isoniazide 300 mg p.o. and pyrazinamide 1500 mg p.o. Unconscious subjects will receive oral drugs via nasogastric tubes (NGT) |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Tuberculous meningitis, diagnosed based on clinical and/or CSF criteria
- Age 15 years old or more
- Hospitalized for the treatment
Key exclusion criteria (6 listed)
- Pregnancy/lactation
- On TB treatment within 7 days before inclusion
- Elevated liver enzyme (> 5x than normal values)
- Known hypersensitivity/intolerance to rifampicin or moxifloxacin
- Prolonged QTc interval in ECG or other detectable cardiac arrythmias, in the absence of hypokalemia
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 |
|---|---|---|
| MoxifloxacinAlso: Avelox (r)Subjects on both arms will further be randomized into receiving moxifloxacin either in standard dose (400 mg p.o.), high dose (800 mg p.o.) of moxifloxacin, or not receiving moxifloxacin (ethambutol 750 mg p.o., instead) Intervention drug will be given for 14 days, and the drug will be switched to ethambutol 750 mg p.o. (in accordance with National TB Program) | Drug | High dose rifampisin, Standard dose rifampisin |
Primary outcome
Rifampicin and Moxifloxacin concentration in plasma and CSF
Time frame: Plasma drug concentration samplings at 0, 1, 2, 4, 6 and 24h post dose (6 time points). CSF samples at 2 time points.
On sampling day (one of the first 3 days of hospitalization), we will measure plasma and CSF drug concentration at several time points. Plasma drug concentration will be measured at 6 time points (hour 0, 1, 2, 4, 6 and 12). CSF drug concentration at 2 time points: (1) hour 3-6 post dose on the same blood sampling day and (2) within 5 days after the 1st day of TB drug administration, 1-3 hours after drug intake
1 secondary outcome
Early and late mortality
Time frame: 1st and 6th month of TB treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2012.
- Derived from this study: PubMed 25703312Te Brake L, Dian S, Ganiem AR, Ruesen C, Burger D, Donders R, Ruslami R, van Crevel R, Aarnoutse R. Pharmacokinetic/pharmacodynamic analysis of an intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis. Int J Antimicrob Agents. 2015 May;45(5):496-503. doi: 10.1016/j.ijantimicag.2014.12.027. Epub 2015 Feb 7.
- Derived from this study: PubMed 23103177Ruslami R, Ganiem AR, Dian S, Apriani L, Achmad TH, van der Ven AJ, Borm G, Aarnoutse RE, van Crevel R. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. Lancet Infect Dis. 2013 Jan;13(1):27-35. doi: 10.1016/S1473-3099(12)70264-5. Epub 2012 Oct 25.
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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.
Rovina Ruslami, PhD principal investigator
Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Moxifloxacin in people with Meningitis, Tuberculous and Pharmacokinetics, run by Universitas Padjadjaran at 1 site in Indonesia.
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 3 inclusion and 6 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: finished, as of the sponsor's last update on 7 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rifampicin and Moxifloxacin concentration in plasma and CSF (time frame: Plasma drug concentration samplings at 0, 1, 2, 4, 6 and 24h post dose (6 time points). CSF samples at 2 time points.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01158755, which also lists 2 linked publications.
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 7 Jun 2012.