Tuberculosis, Multidrug-ResistantPhase 2/3NCT00513396
High-Dose Isoniazid Adjuvant Therapy for Multidrug Resistant Tuberculosis
A Phase 2/3 study testing Isoniazid in people with Tuberculosis, Multidrug-Resistant, run by GSVM Medical College.
Trial summary
The need for a standardized treatment protocol for multidrug resistant tuberculosis (MDR-TB) in resource-limited countries is being increasingly recognized. This single center, double blind, randomized controlled trial was designed to compare the time required for sputum culture conversion and extent of radiological… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, Multidrug-Resistant
- What is being tested?
- Isoniazid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 134 participants
- Where
- No sites listed yet
- Study dates
- Jan 2004to Dec 2006
- Phase
- Phase 2/3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Consecutive patients reporting to the study center
- Sputum-positive for acid-fast bacilli
- HIV-uninfected
- MDR-TB defined as resistance to at least the following two drugs: Isoniazid and Rifampicin.
Who cannot join
- Unwilling to give consent
- Abnormal renal or hepatic profile
- History suggestive of isoniazid hypersensitivity
- Pregnancy
- Lactating mother
- Previous history of taking any of the following: kanamycin, prothionamide, levofloxacin, cycloserine and p-aminosalicylic acid
About this study
Official title: A Randomized Control Trial Of High-Dose Isoniazid Adjuvant Therapy For Multidrug Resistant Tuberculosis
The need for a standardized treatment protocol for multidrug resistant tuberculosis (MDR-TB) in resource-limited countries is being increasingly recognized. This single center, double blind, randomized controlled trial was designed to compare the time required for sputum culture conversion and extent of radiological improvement in cases of MDR pulmonary tuberculosis when isoniazid was included (both at a regular dose and at a high dose) as an adjuvant to the standardized second line of treatment. The study was designed to test the hypothesis that inclusion of high-dose isoniazid will enhance the effectiveness of the second line of treatment in cases of MDR-TB without significantly increasing the toxicity.
Read the detailed description
Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. The global problem of tuberculosis is further complicated by a substantial increase in drug resistant tuberculosis. Available data suggest that drug resistant TB especially multi drug resistant may represent a public health threat in areas with a high prevalence of tuberculosis, suboptimal TB control programmes and/ or HIV. The cure rate of these cases has been reported to be lower than for non-drug resistant TB with a failure rate of 44%. New therapies for MDR-TB have not been introduced since the fluoroquinolones in the 1970s. Strains of Mycobacterium Tuberculosis (M. tub.) in H resistant cases often contain mixture of susceptible \& resistant organisms. Use of high dose H (16- 20 mg/kg) can eliminate susceptible \& those with low level resistance4. This Study was done to evaluate the role of isoniazid (INH) at high \& normal dosages as an adjuvant therapy in treatment of patients with persistent culture positive pulmonary tuberculosis despite 6 months of continuous first line antitubercular treatment and on culture at least resistant to isoniazid and rifampicin.
- Conditions
- Tuberculosis, Multidrug-Resistant
- Being tested
- Isoniazid, Placebo
- Keywords
- Randomized control trial, multidrug resistant tuberculosis, isoniazid, standardized regimen, adjuvant therapy
- Medical subject headings
- Tuberculosis, Multidrug-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsoniazidDrug
High-dose isoniazid (16-18 mg/kg/day) in addition to standardized regimen that included the following: kanamycin (15 mg/kg/day), levofloxacin (7.5-15 mg/kg/day), protionamide (10-20 mg/kg/day), cycloserine (10-20 mg/kg/day) and p-aminosalicylic acid (150 mg/kg/day)
Regular dose isoniazid (5 mg/kg/day) in addition to standard regimen that included the following: kanamycin (15 mg/kg/day), levofloxacin (7.5-15 mg/kg/day), protionamide (10-20 mg/kg/day), cycloserine (10-20 mg/kg/day) and p-aminosalicylic acid (150 mg/kg/day)
PlaceboDrug
Similar appearing and similarly packaged placebo tablets in addition to the standardized regimen that included the following: kanamycin (15 mg/kg/day), levofloxacin (7.5-15 mg/kg/day), protionamide (10-20 mg/kg/day), cycloserine (10-20 mg/kg/day) and p-aminosalicylic acid (150 mg/kg/day)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Isoniazid |
| 2 | Active comparator | Not described Receives: Drug: Isoniazid |
| 3 | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to sputum culture conversion
Measured: 1 year
Secondary outcomes (3)
Extent of radiological improvement
Measured: 1 year
Proportion with peripheral neuropathy
Measured: 1 year
Proportion with hepatotoxicity
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2007 (estimated)
- Study startJan 2004
- Study completionDec 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculosis, Multidrug-ResistantStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- GSVM Medical College
- Sponsor type
- University, hospital or other
- Investigators
- Subodh Katiyar, MD, Study chair, GSVM Medical College, Kanpur, IndiaShivesh Prakash, MBBS, Principal investigator, GSVM Medical College, Kanpur, IndiaShailesh Bihari, MD, Principal investigator, GSVM Medical College, Kanpur, IndiaHemant Kulkarni, MD, Principal investigator, Lata Medical Research Foundation, Nagpur, IndiaManju Mamtani, MD, Principal investigator, Lata Medical Research Foundation, Nagpur, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00513396
- Sponsor's protocol ID
- TB chest - 1/2005
- Status last verified
- Jul 2007
- First submitted
- 6 Aug 2007
- Last updated
- 8 Aug 2007
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Control Trial Of High-Dose Isoniazid Adjuvant Therapy For Multidrug Resistant Tuberculosis
- ClinicalTrials.gov ID
- NCT00513396
- Acronym / sponsor ID
- TB chest - 1/2005
- Conditions
- Tuberculosis, Multidrug-Resistant
- Keywords
- Randomized control trial, multidrug resistant tuberculosis, isoniazid, standardized regimen, adjuvant therapy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 134 participants (actual)
- Lead sponsor
- GSVM Medical CollegeUniversity, hospital or other
- Study start
- Jan 2004
- Study completion
- Dec 2006 (actual)
- First posted
- 8 Aug 2007 (estimated)
- 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.
The need for a standardized treatment protocol for multidrug resistant tuberculosis (MDR-TB) in resource-limited countries is being increasingly recognized. This single center, double blind, randomized controlled trial was designed to compare the time required for sputum culture conversion and extent of radiological improvement in cases of MDR pulmonary tuberculosis when isoniazid was included (both at a regular dose and at a high dose) as an adjuvant to the standardized second line of treatment. The study was designed to test the hypothesis that inclusion of high-dose isoniazid will enhance the effectiveness of the second line of treatment in cases of MDR-TB without significantly increasing the toxicity.
Detailed description
Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. The global problem of tuberculosis is further complicated by a substantial increase in drug resistant tuberculosis. Available data suggest that drug resistant TB especially multi drug resistant may represent a public health threat in areas with a high prevalence of tuberculosis, suboptimal TB control programmes and/ or HIV. The cure rate of these cases has been reported to be lower than for non-drug resistant TB with a failure rate of 44%. New therapies for MDR-TB have not been introduced since the fluoroquinolones in the 1970s. Strains of Mycobacterium Tuberculosis (M. tub.) in H resistant cases often contain mixture of susceptible \& resistant organisms. Use of high dose H (16- 20 mg/kg) can eliminate susceptible \& those with low level resistance4. This Study was done to evaluate the role of isoniazid (INH) at high \& normal dosages as an adjuvant therapy in treatment of patients with persistent culture positive pulmonary tuberculosis despite 6 months of continuous first line antitubercular treatment and on culture at least resistant to isoniazid and rifampicin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Isoniazid |
| 2 | Active comparator | Drug: Isoniazid |
| 3 | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Consecutive patients reporting to the study center
- Sputum-positive for acid-fast bacilli
- HIV-uninfected
- MDR-TB defined as resistance to at least the following two drugs: Isoniazid and Rifampicin.
Key exclusion criteria (6 listed)
- Unwilling to give consent
- Abnormal renal or hepatic profile
- History suggestive of isoniazid hypersensitivity
- Pregnancy
- Lactating mother
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 |
|---|---|---|
| IsoniazidHigh-dose isoniazid (16-18 mg/kg/day) in addition to standardized regimen that included the following: kanamycin (15 mg/kg/day), levofloxacin (7.5-15 mg/kg/day), protionamide (10-20 mg/kg/day), cycloserine (10-20 mg/kg/day) and p-aminosalicylic acid (150 mg/kg/day) Regular dose isoniazid (5 mg/kg/day) in addition to standard regimen that included the following: kanamycin (15 mg/kg/day), levofloxacin (7.5-15 mg/kg/day), protionamide (10-20 mg/kg/day), cycloserine (10-20 mg/kg/day) and p-aminosalicylic acid (150 mg/kg/day) | Drug | 1, 2 |
| PlaceboSimilar appearing and similarly packaged placebo tablets in addition to the standardized regimen that included the following: kanamycin (15 mg/kg/day), levofloxacin (7.5-15 mg/kg/day), protionamide (10-20 mg/kg/day), cycloserine (10-20 mg/kg/day) and p-aminosalicylic acid (150 mg/kg/day) | Drug | 3 |
Primary outcome
Time to sputum culture conversion
Time frame: 1 year
3 secondary outcomes
Extent of radiological improvement
Time frame: 1 year
Proportion with peripheral neuropathy
Time frame: 1 year
Proportion with hepatotoxicity
Time frame: 1 year
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 8 Aug 2007.
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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.
Subodh Katiyar, MD study chair
GSVM Medical College, Kanpur, India
Shivesh Prakash, MBBS principal investigator
GSVM Medical College, Kanpur, India
Shailesh Bihari, MD principal investigator
GSVM Medical College, Kanpur, India
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Isoniazid in people with Tuberculosis, Multidrug-Resistant, run by GSVM Medical College.
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 4 inclusion and 6 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 8 Aug 2007. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Time to sputum culture conversion (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Aug 2007.