Diabetes MellitusPhase 4TBLNCT03278483
Efficacy, Security, Adherence, Tolerability and Cost Effectiveness of Latent TB Treatment in Patients With TB/DM2 (TBL)
A Phase 4 study testing Isoniazid 300 mg Oral Tablet and Rifampin 600 mg Oral Tablet in people with Diabetes Mellitus and Tuberculin (Skin Test) Positive, run by Instituto Nacional de Salud Publica, Mexico at 1 site in Mexico.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Diabetes Mellitus, Tuberculin (Skin Test) Positive
- What is being tested?
- Isoniazid 300 mg Oral Tablet and Rifampin 600 mg Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 396 participants
- Where
- 1 siteMexico
- Study dates
- 28 Feb 2019to 28 Feb 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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.
Who cannot join
- 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
Show all 10Show fewer
- Active hepatopathy
- Grade III or higher peripheral neuropathy
- Chronic alcohol ingestion
- Contacts of patients with isoniazid or rifampicin drug resistance
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Instituto Nacional de Ciencias Medicas y Nutrición
Mexico City, 14000
About this study
Official title: Efficacy, Security, Adherence, Tolerability and Cost Effectiveness of Latent TB Treatment in Patients With TB/DM2
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.
Read the 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.
- Conditions
- Diabetes Mellitus, Tuberculin (Skin Test) Positive
- Being tested
- Isoniazid 300 mg Oral Tablet, Rifampin 600 mg Oral Tablet
- Keywords
- Latent tuberculosis, ,, isoniazid, rifampin,, rifampin,, adverse,, diabetes mellitus
- Medical subject headings
- Diabetes Mellitus, Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isoniazid 300 mg Oral TabletDrug
Also called Isonicotinic acid
Isoniazid tablets 300mg daily plus pyridoxine 50mg daily
Rifampin 600 mg Oral TabletDrug
Also called Rifadin
Rifampin capsules 600mg daily
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Rifampin 600 mg Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 6 months
Adherence
Counting the number of administered pills, adequate adherence is more than 80% of administered pills.
Measured: Up to 6 months
Toxicity (liver function)
Liver function tests
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2017
- Study start28 Feb 2019
- Primary completion28 Feb 2019
- Study completion28 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 396 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Salud Publica, Mexico
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto Nacional de Enfermedades Respiratorias, Instituto Nacional de Ciencias Medicas y Nutrición
- Responsible party
- Principal investigator, Ma. de Lourdes Garcia Garcia, Instituto Nacional de Salud Publica, Mexico
- Investigators
- Jose JS Sifuentes -Osornio, Dr, Principal investigator, Instituto Nacional de Ciencias Médcias y NutriciónMartha MT Torres-Rojas, DCs, Principal investigator, Instituto Nacional de Enfermedades Respiratorias
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03278483
- Sponsor's protocol ID
- 1341
- Acronym
- TBL
- Status last verified
- Apr 2019
- First submitted
- 7 Aug 2017
- Last updated
- 26 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 25359354
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy, Security, Adherence, Tolerability and Cost Effectiveness of Latent TB Treatment in Patients With TB/DM2
- ClinicalTrials.gov ID
- NCT03278483
- Acronym / sponsor ID
- TBL / 1341
- Conditions
- Diabetes Mellitus, Tuberculin (Skin Test) Positive
- Keywords
- Latent tuberculosis, ,, isoniazid, rifampin,, rifampin,, adverse,, diabetes mellitus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 396 participants (actual)
- Lead sponsor
- Instituto Nacional de Salud Publica, MexicoUniversity, hospital or other
- Collaborators
- Instituto Nacional de Enfermedades Respiratorias, Instituto Nacional de Ciencias Medicas y Nutrición
- Study start
- 28 Feb 2019 (actual)
- Primary completion
- 28 Feb 2019 (actual)
- Study completion
- 28 Feb 2019 (actual)
- First posted
- 11 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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
| Arm | Type | Receives |
|---|---|---|
| Isoniazid | Active comparator | Drug: Isoniazid 300 mg Oral TabletDiabetic 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 |
| Rifampin | Active comparator | Drug: Rifampin 600 mg Oral TabletDiabetic patients with a positive TST of >10mm, who wil be randomly assigned to receive treatment with rifampin 600mg Oral Tablets daily for three months |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isoniazid 300 mg Oral TabletAlso: Isonicotinic acidIsoniazid tablets 300mg daily plus pyridoxine 50mg daily | Drug | Isoniazid |
| Rifampin 600 mg Oral TabletAlso: RifadinRifampin capsules 600mg daily | Drug | Rifampin |
Primary outcome
Efficacy of treatment with rifampicin compared to efficacy of treatment with isoniazid
Time frame: Up to 18 months
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.
Toxicity (neuropathy)
Time frame: Up to 6 months
Neurological alterations will be assessed using the Michigan questionnaire and in a subsample they will evaluate neuropathy using electroneurography.
Adherence
Time frame: Up to 6 months
Counting the number of administered pills, adequate adherence is more than 80% of administered pills.
Toxicity (liver function)
Time frame: Up to 6 months
Liver function tests
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2019.
- Results publication: PubMed 25359354Torres 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jose JS Sifuentes -Osornio, Dr principal investigator
Instituto Nacional de Ciencias Médcias y Nutrición
Martha MT Torres-Rojas, DCs principal investigator
Instituto Nacional de Enfermedades Respiratorias
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Isoniazid 300 mg Oral Tablet and Rifampin 600 mg Oral Tablet in people with Diabetes Mellitus and Tuberculin (Skin Test) Positive, run by Instituto Nacional de Salud Publica, Mexico at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of treatment with rifampicin compared to efficacy of treatment with isoniazid (time frame: Up to 18 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03278483, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2019.