Pharmacokinetics of Anti-tuberculosis Drugs in Gastrectomized Patients

Absorption of Anti-tuberculosis Drugs and Its Effect to Treatment Response in Gastrectomized Patients

The purpose of this study is to evaluate the effect of gastrectomy on pharmacokinetic profile of first-line anti-tuberculosis drugs in patients with pulmonary tuberculosis (TB).

Study Overview

• Status: Completed
• Conditions: Early Gastric Cancer; Tuberculosis; Tuberculosis, Pulmonary
• Intervention / Treatment: Drug: standard first line anti-TB drugs

Detailed Description

Gastrectomy is a well-known risk factor for TB. Also, there were some reports about malabsorption of anti-TB drugs in the gastrectomized patients. However, pharmacokinetics of recently used first line anti-TB drugs in the gastrectomized patients have not been well evaluated simultaneously. Therefore, the investigators aim to evaluate the effect of gastrectomy on pharmacokinetic profile of first-line anti-TB drugs in patients with pulmonary TB through this study.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
      • Respiratory Clinic, National Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Among patients with pulmonary TB diagnosed in our hospital and treated with 4 first line anti-TB drug(isoniazid/rifampicin/ethambutol/pyrazinamide= HREZ), we recruit patients who underwent gastrectomy to Gastrectomy group. And then, we recruit age-sex matched patients who did not underwent gastrectomy to Non-gastrectomy group.(age ±3 years)

Description

Inclusion Criteria:

1. Age greater than 18 years and less than 80 years
2. pulmonary TB confirmed by microbiologic test such as AFB culture or TB PCR
3. usage of 4 first-line anti-TB drugs (Isoniazid(INH) Rifampin(RFP) Ethambutol(EMB), Pyrazinamide(PZA) = HREZ)

Exclusion Criteria:

1. patients with liver disease (bilirubin ≥ 1.5 mg/d or AST ≥ 2 x normal upper limit) or chronic renal failure (Cr ≥ 2.0 mg/d) who cannot use first-line anti-TB drugs
2. patients with AIDS or hypoalbuminemia(albumin < 3.0g/dl)that will influence pharmacokinetics of first line anti-TB drugs
3. patients using other drugs that will influence pharmacokinetics of first line anti-TB drugs during anti-TB treatment (e.g warfarin)
4. patients using anti-cancer or immunosuppressive agents that will influence the response of pulmonary TB to anti-TB drugs
5. discontinuation of first-line anti-TB drugs(HREZ)due to side effect or resistance
6. follow-up loss before completion of anti-TB treatment
7. any condition making the patients undergo gastrectomy during anti-TB treatment in case of Non-gastrectomy group

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Gastrectomy; Twenty gastrectomized patients with pulmonary TB, treated with standard first line anti-TB drugs(isoniazid/rifampicin/ethambutol/pyrazinamide), administered daily, orally	Drug: standard first line anti-TB drugs; We will perform pharmacokinetic study in gastrectomy and non-gastrectomy group, to evaluate the effect of gastrectomy on pharmacokinetic profile of first-line anti-TB drugs in patients with TB; Other Names: Pharmacokinetics of Anti-tuberculosis Drugs
Non-gastrectomy; Twenty non-gastrectomized patients with pulmonary TB, treated with standard first line anti-TB drugs(isoniazid/rifampicin/ethambutol/pyrazinamide), administered daily, orally	Drug: standard first line anti-TB drugs; We will perform pharmacokinetic study in gastrectomy and non-gastrectomy group, to evaluate the effect of gastrectomy on pharmacokinetic profile of first-line anti-TB drugs in patients with TB; Other Names: Pharmacokinetics of Anti-tuberculosis Drugs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The change in the maximum concentration (Cmax) of first-line TB drugs	Before and 1, 2, 4, 6 and 8 hours after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effects of pharmacokinetics on responses of pulmonary TB to anti-TB drug	Treatment duration can be varied according to several factors such as a first TB episode or not, cavitary TB, and AFB culture(+) after 2month-treatment etc. We will plan 6 or 9 months treatment for each patient according to these factors. During treatment period, we will check chest radiographs and sputum AFB smear/culture with every 2-3month intervals. At 9month after treatment, we will evaluate the effects of pharmacokinetics on responses of pulmonary TB to anti-TB drug by taking account of improvement on chest radiograph and negative conversion and its continuation on sputum smear/culture.	9month after anti-TB treatment

Collaborators and Investigators

• Sponsor: National Cancer Center, Korea
• Investigators: Principal Investigator: HEE SEOK LEE, M.D., National Cancer Center

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: May 23, 2011
• First Submitted That Met QC Criteria: June 1, 2011
• First Posted (Estimate): June 2, 2011

Study Record Updates

• Last Update Posted (Actual): September 25, 2020
• Last Update Submitted That Met QC Criteria: September 24, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: pharmacokinetics; tuberculosis; gastrectomy; first-line drugs
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary; Anti-Infective Agents; Anti-Bacterial Agents; Antitubercular Agents
• Other Study ID Numbers: NCCCTS-10-493