Rifampicin Explorative PK Study for Tuberculous Meningitis Comparing Oral and Intravenous Preparation

NCT01802502 | Completed Phase 2 DMC

• 1 other identifier: TB-201302.01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Tuberculous (TB) meningitis is the most severe manifestation of TB infection, leaving up to 50% of patients dead or neurologically disabled. Current treatment is similar to treatment of lung TB, although penetration of some antibiotics into the brain is poor and the immune-pathology of TB meningitis is very different from pulmonary TB. In a recent phase II clinical trial from the investigators group, the first of its kind globally, intensified antibiotic treatment, with moxifloxacin and high dose rifampicin, strongly reduced mortality of TB meningitis. The investigators aim to examine the effect of intensified antibiotic treatment on mortality and morbidity of TB meningitis in a phase 3 clinical trial, preceded with an explorative pharmacokinetic (PK) study to examine if higher oral doses rifampicin result in exposures similar to the i.v. dose used in our phase 2 trial, since oral rifampicin could be implemented much easier in low-resource settings.

Conditions

Tuberculous Meningitis

Keywords

tuberculous meningitis; rifampicin; bioequivalence; oral administration; intravenous administration

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic profile of several rifampicin dose

  We will measure plasma drug concentration at hour 0, 1, 2, 4, 8, and 12, while CSF drug concentration will be measured at a single time point i.e. at hour 3-6 post dose. The sampling days will be (1) within the first three days, and (2) at day 14 of the intensified treatment.

  Day 2 and Day 14; 6 time points for blood analysis, and 1 time point for CSF analysis

Secondary Outcomes (1)

• mortality

  early (1 month) and late (6 months)

Study Arms (3)

Rifampicin 600 mg

ACTIVE COMPARATOR

Subjects in this arm receive 600 mg rifampicin intravenously

Drug: Rifampicin intravenous

rifampicin 750 mg

EXPERIMENTAL

Subjects in this arm receive 750 mg rifampicin orally

Drug: Oral rifampicin

rifampicin 900 mg

EXPERIMENTAL

Subjects in this arm receive rifampicin 900 mg orally

Drug: Oral rifampicin

Interventions

Rifampicin intravenous DRUG

Also known as: Rifadin

Rifampicin 600 mg

Oral rifampicin DRUG

Also known as: Rifampisin (Kimia Farma, Bandung, Indonesia)

rifampicin 750 mg; rifampicin 900 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• Probable/possible tuberculosis meningitis using uniform case definition
• Agree to participate in the study

You may not qualify if:

• Patient with antituberculosis treatment within last 2 weeks.
• Increase liver function \>5x upper limit of normal
• Pregnancy

Sponsors & Collaborators

• Universitas Padjadjaran: lead
• Radboud University Medical Center: collaborator

Study Sites (1)

Hasan Sadikin Hospital

Bandung, West Java, 40122, Indonesia

Location

Related Publications (2)

• Ruslami 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.

  PMID: 23103177 BACKGROUND

• Marais S, Thwaites G, Schoeman JF, Torok ME, Misra UK, Prasad K, Donald PR, Wilkinson RJ, Marais BJ. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis. 2010 Nov;10(11):803-12. doi: 10.1016/S1473-3099(10)70138-9. Epub 2010 Sep 6.

  PMID: 20822958 BACKGROUND

MeSH Terms

Conditions

Tuberculosis, Meningeal

Interventions

Rifampin

Condition Hierarchy (Ancestors)

Meningitis, Bacterial; Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Tuberculosis, Central Nervous System; Tuberculosis, Extrapulmonary; Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Rovina Ruslami, M.D., PhD

  Faculty of Medicine Universitas Padjadjaran - Dr. Hasan Sadikin Hospital Bandung

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2013
• First Posted: March 1, 2013
• Study Start: June 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: April 1, 2014
• Last Updated: June 17, 2014

Record last verified: 2014-06

Locations

ID (1)