Efficacy, Security, Adherence, Tolerability and Cost Effectiveness of Latent TB Treatment in Patients With TB/DM2 (TBL)
Condition: Diabetes Mellitus; Tuberculin (Skin Test) Positive
MeSH terms: Diabetes Mellitus
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      This study is a randomized control trial, with two parallel arms, fixed assignment, fixed
      sample size and in two study sites. Participants will be assigned 1:1 to receive one of the
      two treatment regimens: isoniazid for 6 months or rifampicin for 3 months. The assignment
      will be fixed because the covariates that predict the clinical outcome and the accumulated
      outcome of participants will not affect treatment assignment. In patients that the Michigan
      evaluation identifies as having neuropathic changes researchers will perform an
      electroneurography in order to identify the degree of neuropathy if any. This will be
      performed in the neurophysiology lab of the INCMNSZ. An independent comity will monitor
      adverse events.

      Sample size It is necessary to include 193 participants, for each arm; this includes a 20%
      increase to compensate loss during follow up. This will provide a power equal or higher than
      80% considering an alpha of 0.05 (.25 at two tails) in order to answer to each one of the
      following objectives.

      Latent tuberculosis treatment with isoniazid is the gold standard and given its efficacy it
      would not be ethical to propose a placebo group. Researchers hypothesize that treatment with
      rifampicin will not be inferior in efficacy (measured using the response of biomarkers) and
      will be equivalent in toxicity to that observed with isoniazid treatment.

      Subjects will be asked to attend on the 15th and 30th of the month and then once a month till
      the end of treatment. In case a patient does not assist, researchers will carry out a home
      visit.

      Clinical, microbiological and metabolic evaluation

      Researchers will apply a validated questionnaire that explores sociodemographic,
      epidemiological and clinical information as well as a questionnaire developed by the
      researchers that captures information of DM2 long term complications. The Michigan
      questionnaire will be applied using the NCI-CTC scale in version 3 for neuropathic symptoms
      as well as an evaluation with a Semmes-Weinstein monofilament of 5.07/10gr in 4 points of the
      sole of each foot:

        -  Distal phalange of the 1st toe, base of the 1st metatarsal and base of the 3rd
           metatarsal

        -  Base of the 5th metatarsal In a subsample researchers will carry out an
           electroneurography study in order to measure and document the level of likely damage as
           an adverse event.

      Tuberculin Skin Test (TST) In patients with DM2 researchers will apply TST using the Mantoux
      technique. Reactivity will be measured with the diameter of the induration at 48 and 72
      hours. Patients with a TST>10mm will be randomized to the trail.

      Chest X ray All patients with a positive TST will have a chest X ray taken which will be
      evaluated by a pulmonologist in order to exclude millar TB.

      All patients will be tested for hematic cytology, glucose, glycosylated hemoglobin, and
      creatinine and liver tests. All lab tests will be carried out using standardized methods that
      are commercially available.

      All documentation of clinical evaluations will be included in the patient's medical chart.
      These will be safeguarded by the main researcher and confidentiality will be protected at all
      times.

      TB tests During follow up respiratory symptoms will be evaluated. Patients with respiratory
      symptoms of more than 2 weeks will be asked to give 3 sputum samples in order to analyze for
      acid fast bacilli (AFB) and Mycobacterium tuberculosis (MTB) culture using standardized
      methods.

      All samples will be identified with a code that links the sample with clinical and
      epidemiological data. Researchers have established a system that prevents unauthorized people
      from accessing the samples and personal data.

      Field work Personnel have been trained in the good clinical practice course which Works very
      closely with the health centers. Activities are monitored by supervisors that have been
      trained to insure the coordination of activities and quality control.

      Independent comity for monitoring adverse events For this study researchers will integrate an
      independent comity to monitor adverse events, which will revise all adverse events and will
      give follow up.
    

Intervention name(s): Isoniazid 300 mg Oral Tablet; Rifampin 600 mg Oral Tablet
Intervention type(s): Drug; Drug
Intervention description(s): Isoniazid tablets 300mg daily plus pyridoxine 50mg daily; Rifampin capsules 600mg daily
Other intervention name(s): Isonicotinic acid; Rifadin
Intervention MeSH terms: Rifampin; Isoniazid
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 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
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Latent tuberculosis, ,; isoniazid, rifampin,; rifampin,; adverse,; diabetes mellitus