Phase II study: drug exposure and safety of an shortened tuberculosis treatment based on higher doses of Rifampicin and Pyrazinamide

Phase 1

• Conditions: Tuberculosis; MedDRA version: 20.0Level: PTClassification code 10044755Term: TuberculosisSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2019-003721-25-SE
• Lead Sponsor: Region Östergötland

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-12-16
• Last Update Posted: 16 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1) Patient> 18 years
2) Confirmed active lung TB by positive culture or positive PCR for the M.tuberculosis complex.
3) Planned to start on active TB treatment (first line) but not yet started treatment.
4) HIV negative
5) BMI> 17
6) Have given written consent.
7) Fertile women should use adequate non-hormonal contraceptives such as a condom and submit to a serum negative pregnancy test if the woman is not postmenopausal. Female patients are not considered fertile if they are post-menopausal, without menstruation for the last 12 months or surgically sterile (bilateral oophorectomy, hysterectomy, tubal ligation 12 months before study start).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 38
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

1) The research person is not able to give informed consent or is considered so affected by his illness that he or she is unable to understand the study information.
2) Other concurrent infectious disease requiring active treatment.
3) Known hypersensitivity to rifamycin, isoniazid, pyrazinamide, etambutol hydrochloride and / or to any of the excipients listed in section Summary of Product Characteristics or previous serious adverse reaction to RIF, INH, PZA or EMB.
4) Contraindications according to the summary of product characteristics of RIF, INH, PZA or EMB:
• Known hypersensitivity according to exclusion criterion 3 above and severe renal failure (creatinine clearance <30 ml / min) which coincides with exclusion criterion 13 below.
• Previously drug-induced liver inflammation
• Previous acute liver diseases regardless of cause
• Acute liver disease regardless of cause
• Severe liver disease
• Porphyria
• Previously serious adverse reactions when treated with any of the drugs such as drug-induced fever, chills or arthritis
• Concomitant use of drugs whose therapeutic efficacy is very important for the patient whose plasma concentrations are markedly lowered by RIF, and where compensatory dose adjustments to maintain efficacy cannot be made, such as voriconazole, nifedipine, artemeter-lumefantrine and protease inhibitors (see section FASS Interactions)
• Manifest Icterus
• Acute arthritis
5) Treated for active TB in the last year before inclusion.
6) Resistance to any of the drugs (RIF, INH, PZA, EMB) included in standard tbc treatment according to molecular biological or phenotypic resistance assay.
7) Miliary tuberculosis
8) Pulmonary tuberculosis with any of the following:
(a) the presence of copious amounts of acid-fast rods (grade 3) in any of the clinical sputum tests
(b) pulmonary x-ray changes graded to advanced TB (according to the National Tuberculosis Association, 1961)
9) Extra-pulmonary tuberculosis without simultaneous pulmonary tuberculosis.
10) Pregnancy and breastfeeding.
11) Immunosuppression (known primary or secondary immunodeficiency including immunosuppressive treatment such as cytostatics, immunomodulatory therapy,> / = 15 mg prednisolone or equivalent cortisone dose)
12) Heart failure fulfilling NYHA Class III or IV
13) Renal failure with estimated GFR <50 mL / min (according to accredited laboratory method)
14) Not well-regulated diabetes mellitus with HbA1c> 62 mmol /mol for type I diabetes and HbA1c> 52 mmol /mol for type II diabetes.
15) Known liver disease including hepatitis and elevated liver transaminases (transaminases> x1.5 of the reference value).
16) Alcohol and / or drug dependence based on patient history.
17) A research person who the investigator after discussing with the study leader, forother reasons than the above, is deemed not suitable for inclusion.
18) Weight <35 kg or> 90 kg at inclusion
19) Patient participated in a clinical trial within 30 days prior to inclusion.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified