Efficacy, Security, Adherence, Tolerability and Cost Effectiveness of Latent TB Treatment in Patients With TB/DM2 (TBL)

NCT03278483 | Completed Phase 4 DMC

• 1 other identifier: 1341
• Study Type: interventional
• Target: 396
• Locations: 1 country
• Sites: 1

Brief Summary

Researchers will evaluate the efficacy, toxicity, adherence and cost effectiveness of treatment with isoniazid or rifampicin in patients with diabetes mellitus type two (DM2) and latent TB (LTB). This is a collaborative study with participation from three national institutes (Instituto Nacional de Salud Pública (INSP), Instituto Nacional de Enfermedades Respiratorias (INER) and the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran (INCMNSZ)). The study will take place in the VII sanitary jurisdiction of Orizaba and the INCMNSZ that has the necessary infrastructure and human resources. Researchers will evaluate 3000 patients with diabetes using a standardized questionnaire and a tuberculin skin test (TST) test. Eligible patients will be invited to participate and from those that agree to participate and sign a written informed consent we will obtain clinical, epidemiological, nutritional and metabolic information. Patients with altered liver function tests will be excluded.

Conditions

Diabetes Mellitus; Tuberculin (Skin Test) Positive

Keywords

Latent tuberculosis, ,; isoniazid, rifampin,; rifampin,; adverse,; diabetes mellitus

Outcome Measures

Primary Outcomes (4)

• Efficacy of treatment with rifampicin compared to efficacy of treatment with isoniazid

  Researchers will measure with ELISA in vitro production of interferon gamma of peripheric mononuclear cels as a response to stimuli by RV0849 and RV1737 antigens. The cut of value is of \>100pg/ml.

  Up to 18 months

• Toxicity (neuropathy)

  Neurological alterations will be assessed using the Michigan questionnaire and in a subsample they will evaluate neuropathy using electroneurography.

  Up to 6 months

• Adherence

  Counting the number of administered pills, adequate adherence is more than 80% of administered pills.

  Up to 6 months

• Toxicity (liver function)

  Liver function tests

  Up to 6 months

Study Arms (2)

Isoniazid

ACTIVE COMPARATOR

Diabetic patients with a positive TST of \>10mm, will be randomly assigned to receive treatment with isoniazid 300mg Oral Tablet daily plus pyridoxine 50mg daily for six months

Drug: Isoniazid 300 mg Oral Tablet

Rifampin

ACTIVE COMPARATOR

Diabetic patients with a positive TST of \>10mm, who wil be randomly assigned to receive treatment with rifampin 600mg Oral Tablets daily for three months

Drug: Rifampin 600 mg Oral Tablet

Interventions

Isoniazid 300 mg Oral Tablet DRUG

Isoniazid tablets 300mg daily plus pyridoxine 50mg daily

Also known as: Isonicotinic acid

Isoniazid

Rifampin 600 mg Oral Tablet DRUG

Rifampin capsules 600mg daily

Also known as: Rifadin

Rifampin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes mellitus (DM2) diagnosed based on the National Official Norm
• respiratory symptoms
• Tuberculin Skin Test (TST) \>10mm of induration
• chest X ray without pleural, lung or mediastinal lesions
• hemoglobin \< 8 gm/dl
• platelets \> 60,000 per microliter
• bilirubin \< 2.5 mg/dl
• Aspartate aminotransferase (AST) , Glutamic oxalacetic transaminases (SGOT) and alkaline phosphatase less than twice the normal value
• negative pregnancy test
• negative Human immunodeficiency virus infection test (HIV test)
• signed written informed consent.

You may not qualify if:

• Attending selected cites
• Respiratory symptoms defined as cough with or without sputum for more than 2 weeks
• Evidence or clinical suspicion of active tuberculosis (TB)
• Current treatment with antituberculous drugs
• History of having received more than one month's treatment for latent Tuberculosis (LTB) or antituberculous drugs
• Hypersensitivity or intolerance to isoniazid or rifampicin
• Active hepatopathy
• Grade III or higher peripheral neuropathy
• Chronic alcohol ingestion
• Contacts of patients with isoniazid or rifampicin drug resistance

Sponsors & Collaborators

• Instituto Nacional de Salud Publica, Mexico: lead
• Instituto Nacional de Enfermedades Respiratorias: collaborator
• Instituto Nacional de Ciencias Medicas y Nutrición: collaborator

Study Sites (1)

Instituto Nacional de Ciencias Medicas y Nutrición

Mexico City, 14000, Mexico

Location

Related Publications (1)

• Torres M, Garcia-Garcia L, Cruz-Hervert P, Guio H, Carranza C, Ferreyra-Reyes L, Canizales S, Molina S, Ferreira-Guerrero E, Tellez N, Montero-Campos R, Delgado-Sanchez G, Mongua-Rodriguez N, Sifuentes-Osornio J, Ponce-de Leon A, Sada E, Young DB, Wilkinson RJ. Effect of isoniazid on antigen-specific interferon-gamma secretion in latent tuberculosis. Eur Respir J. 2015 Feb;45(2):473-82. doi: 10.1183/09031936.00123314. Epub 2014 Oct 30.

  PMID: 25359354 RESULT

MeSH Terms

Conditions

Diabetes Mellitus; Latent Tuberculosis

Interventions

Isoniazid; Tablets; Isonicotinic Acids; Rifampin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Dosage Forms; Pharmaceutical Preparations; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Jose JS Sifuentes -Osornio, Dr

  Instituto Nacional de Ciencias Médcias y Nutrición

  PRINCIPAL INVESTIGATOR

• Martha MT Torres-Rojas, DCs

  Instituto Nacional de Enfermedades Respiratorias

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of prevention of infectious diseases

Model Details: * Arm Isoniacid Diabetic patients with a positive TST of \>10mm, who wil be randomly assigned to receive treatment with isoniazid tablets 300mg daily plus pyridoxine 50mg daily * Arm B Diabetic patients with a positive TST of \>10mm, who wil be randomly assigned to receive treatment with rifampin capsules 600mg daily

Study Record Dates

• First Submitted: August 7, 2017
• First Posted: September 11, 2017
• Study Start: February 28, 2019
• Primary Completion: February 28, 2019
• Study Completion: February 28, 2019
• Last Updated: April 26, 2019

Record last verified: 2019-04

Locations

ME (1)