Intensified Treatment Regimens for TB Meningitis: PK, PD and Tolerability Study

This study has been completed.
Sponsor:
Collaborator:
Radboud University
Information provided by (Responsible Party):
Ahmad Rizal Ganiem, Universitas Padjadjaran
ClinicalTrials.gov Identifier:
NCT01158755
First received: July 7, 2010
Last updated: June 6, 2012
Last verified: June 2012

July 7, 2010
June 6, 2012
October 2010
December 2011   (final data collection date for 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. ] [ Designated as safety issue: Yes ]

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

Rifampicin and Moxifloxacin concentration in plasma and CSF [ Time Frame: Plasma drug concentration at 4 time points (hour 0, 2, 4, and 6), while CSF concentration at a single time point (hour 3) of the sampling day ] [ Designated as safety issue: Yes ]
We will measure plasma and CSF drug concentration at several time points. The sampling day will be day 2 of hospitalization. Plasma drug concentration will be measured at 4 time points (hour 0, 2, 4, and 6), while CSF concentration at a single time point (hour 3) from the administration of the allocated drug on the sampling day
Complete list of historical versions of study NCT01158755 on ClinicalTrials.gov Archive Site
Early and late mortality [ Time Frame: 1st and 6th month of TB treatment ] [ Designated as safety issue: No ]
We will measure early (within first month of TB treatment) and late (after 6 months of TB treatment) mortality
Same as current
Not Provided
Not Provided
 
Intensified Treatment Regimens for TB Meningitis: PK, PD and Tolerability Study
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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Meningitis, Tuberculous
  • Pharmacokinetics
  • Pharmacodynamics
  • Tolerability
Drug: Moxifloxacin
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)
Other Name: Avelox (r)
  • Active Comparator: Standard dose rifampisin

    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)

    Intervention: Drug: Moxifloxacin
  • Experimental: High dose rifampisin

    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)

    Intervention: Drug: Moxifloxacin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
June 2012
December 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Tuberculous meningitis, diagnosed based on clinical and/or CSF criteria
  • Age 15 years old or more
  • Hospitalized for the treatment

Exclusion Criteria:

  • 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
Both
15 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Indonesia
 
NCT01158755
TB-201006.01
Yes
Ahmad Rizal Ganiem, Universitas Padjadjaran
Universitas Padjadjaran
Radboud University
Principal Investigator: Rovina Ruslami, PhD Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
Universitas Padjadjaran
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP