AzTrials
AzTrials

Pre-Extensively Drug-Resistant Pulmonary TBPhase 3mBPaLNCT05040126

Modified BPaL Regimen for Managing Pre-XDR TB and MDR (TI/NR) TB in India

A Phase 3 study testing Linezolid, Bedaquiline and Pretomanid in people with Pre-Extensively Drug-Resistant Pulmonary TB and Treatment Intolerant Multidrug-Resistant Pulmonary TB, run by Tuberculosis Research Centre, India at 1 site in India.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

Existing problem with DR TB management: Injectable regimens for longer duration with toxicity Poor adherence, treatment failures, continued transmission Need of the study: Oral regimens of shorter duration Improved treatment adherence Implementation of community-based models of care Reduction in direct costs and… Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Linezolid, Bedaquiline and Pretomanid
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
400 participants
Where
1 siteIndia
Study dates
7 Oct 2021to 31 Dec 2024
Phase
Phase 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 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adults aged between 18 years - 65 years
  • Pulmonary Pre-XDR-TB, patients [with documented evidence of resistance to rifampicin with or without isoniazid resistance AND additional resistance to any fluoroquinolones by conventional DST (culture-based1) or rapid DST (Xpert MTB/RIF or Trunat MTB/RIF or LPA) from a certified laboratory] OR MDR-TBTI/NR patients [with documented treatment intolerance or non-response to MDR TB treatment regimen for 6-months or more when the participant was adherent to the treatment regimen]
  • Bodyweight of ≥30 kg (in light clothing and no shoes)
  • Provide written, informed consent before all study-related procedures
  • Provide consent to HIV testing2 (if an HIV test was performed within 1 month before the study start, it should not be repeated as long as documentation can be provided [ELISA and/or Western Blot]).
  • Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) < 2.5 x ULN; Total bilirubin lesser than ULN when accompanied by an increase in other liver function tests.
  • QTcF less than or equal to 450 at baseline
  • Female patients should not be pregnant or should be using a birth control method. They should be willing to continue practicing birth control methods (barrier or non-barrier contraceptive methods including oral contraceptives) throughout the treatment period, or history of post-menopausal for the past 12 months.

Who cannot join

  • Non-DST based criteria
  • Intolerance or risk of toxicity from medicine in the treatment regimens (e.g. drug-drug interactions)
  • Patient who has received more than 2 weeks of Bedaquiline or Linezolid before the first dose of BPaL regimen
  • Pregnancy or Lactating women
  • All forms of Extrapulmonary TB (Lymph node TB associated with Pulmonary DR-TB and pleural effusion associated with pulmonary TB can be considered for inclusion )
  • HIV infected patient having a CD4+ cell count of ≤ 50 cells/µL;
Show all 19Show fewer
  • Currently having an uncontrolled cardiac arrhythmia that requires medication
  • Have any of the following QTcF interval characteristics at screening:
  • QTcF ≥ 450 at baseline \& normal electrolytes, ECG to be repeated after 6 hours and if both ECGs show QTc>450 then the patient should not be challenged with cardiotoxic drugs.
  • History of additional risk factors for Torsade de Pointes, e.g. heart failure, hypokalaemia, family history of long QT syndrome;
  • Any condition in the Investigator's opinion (i.e., an unstable disease such as uncontrolled diabetes on insulin3 or cardiomyopathy), where participation would compromise the well-being of the patient or prevent, limit or confound protocol-specified assessments.
  • Very seriously ill patients (Karnofsky scores < 50 within last 30 days)
  • If results of the serum chemistry panel or, hematology are outside the normal reference range (as given below), the patient may still be considered if the physician judges that the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable.
  • Hypokalaemia, hypomagnesemia, and hypocalcemia should be corrected before a patient receiving any cardiotoxic drugs. (hypothyroidism is not exclusion criteria, to be considered with simultaneous thyroxine replacement therapy and close monitoring)
  • Haemoglobin level of < 9.0 g/dl or Platelet count <1,00,000 /mm3
  • Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) >2.5 x ULN; Total bilirubin greater ULN when accompanied by an increase in other liver function tests
  • Grade III or IV peripheral neuropathy
  • DST based criteria
  • if the result for DST (FQ, LZD)4 is not available and h/o more than 2 weeks consumption of drugs used in the study regimen

Trial locations and contacts

1 site in 1 country.

India1 site

  • S N Medical College

    Agra, Uttar Pradesh

Other trials in India

About this study

Official title: Evaluate the Effectiveness, Safety and Tolerability of Various Doses of Linezolid in Combination With Bedaquiline and Pretomanid in Adults With Pre-Extensively Drug-Resistant (Pre-XDR), Or Treatment Intolerant/Non-responsive Multidrug-Resistant (MDRTI/NR) Pulmonary Tuberculosis in India

Existing problem with DR TB management:

Injectable regimens for longer duration with toxicity Poor adherence, treatment failures, continued transmission

Need of the study:

Oral regimens of shorter duration Improved treatment adherence Implementation of community-based models of care Reduction in direct costs and indirect costs of patients Improved treatment outcomes

Need for shorter, tolerable and effective regimen

Hence modified BPaL regimen is designed to study the newer shorter oral in varying doses of Linezolid for pre XDR Tb patients and MDR TI/NR patients

Read the detailed description

The regimen proposed is based on the NIX-TB and ZeNIX trial regimen with modification in the Linezolid doses. The rationale is -

  1. While the EBA study showed that a modestly greater bactericidal effect over 14 days at the highest 1200 mg daily, this dose appears to be associated with a greater incidence of neuropathic and myelosuppressive effects than the 600 mg daily dose in the NIXTB trial.
  2. Linezolid EBA study showed similar bactericidal activity over 14 days irrespective of the single daily dose or twice-daily doses. A single daily dose will enhance patient adherence and will reduce the total time of exposure to the drug concentration that is greater than the calculated concentration associated with mitochondrial toxicity (likely mechanism for the toxicities of peripheral neuropathy and myelosuppression).
  3. While a full 6 months of linezolid therapy in the regimen may give greater culture conversion and avoid relapse, the mouse model found that linezolid dosing only for one or two months, when B and Pa were given continuously for a total of 3 months, maximized relapse-free cure.
  4. More than 2 months of linezolid, when combined with B and Pa, does not increase relapse-free cure in the mouse model. Thus, the treatment arms in this study will give randomized comparative information about the optimal duration and dose of linezolid in the regimen relative to efficacy and toxicity.
  5. The ZeNIX study with consistent dosing of bedaquilline and pretomanid reported 93% success rate with linezolid 1200 mg for 6 months and 91% with linezolid 600mg for 6 months. However 2 months of 600mg linezolid showed a success rate of 84%. Adverse reactions were reported in 38 % of those receiving 1200mg linezolid for 6 months, 24% of those receiving 600mg of linezolid for 6 months and 13% of those receiving 600mg linezolid for 2 months.
  6. Interim analysis of BEAT study (personal communication/52nd UNION abstract) with 6 month regimen of bedaquilline, delaminid, clofazimine and linezolid (600mg daily for 6 months) reported 89.6% success rate at the end of 6 months of treatment. Adverse reactions such as peripheral neuropathy were reported in 39% and myelosuppression in 47% of the patients.

Learning from ZeNIX and BEAT study, a planned reduction of Linezolid along with BDQ and Pretomanid is planned as BDQ+Pa+LZD 600mg for 9 weeks followed by 300 mg for 17 weeks and BDQ+Pa+LZD 600mg for 13 weeks followed by 300mg for 13 weeks. This will help in deciding the effective dosing of Lzd to be combined with Bdq and Pa for drug resistant TB in the program.

Being tested
Linezolid, Bedaquiline, Pretomanid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LinezolidDrug

    Participants will have a screening period of up to 14 days and will be randomized to one of the study arms in the ratio of 1:1:1, using an interactive web response system.

    Each participant will receive 26 weeks of treatment. If the participant's 16th-week sample remains culture positive, treatment will be extended up to 39 weeks.

    Participants will be followed for 48 weeks after the end of treatment

  • BedaquilineDrug

    Bedaquiline will be administered as four 100 mg tablets (400 mg) by mouth once a day for 2 weeks, followed by two 100 mg tablets (200 mg) by mouth three times a week for 24 weeks in all three arms

  • PretomanidDrug

    Pretomanid is administered as one tablet once a day for 26 weeks in all three arms

Study groups in NCT05040126
Study groupRoleWhat they receive
Arm 1 - 26 weeks of BDQ +Pa + LZD (600mg)Active comparator26 wks. of BDQ +Pa + LZD (600mg) Bedaquiline (available as 100 mg tablets) Bedaquiline will be administered as four 100 mg tablets (400 mg) by mouth once a day for 2 weeks, followed by two 100 mg tablets (200 mg) by mouth three times a week for 24 weeks. Linezolid: (available as 600 mg tablets) - Linezolid will be administered as one 600 mg tablet once daily in Arm1. Pretomanid: (Available as 200 mg tablets): Pretomanid is administered as one tablet once a day for 26 weeks along with Bedaquiline and Linezolid.
Receives: Drug: Linezolid; Drug: Bedaquiline; Drug: Pretomanid
Arm 2 - 9 weeks. of BDQ +Pa + LZD (600mg) followed by 17 wks. of BDQ +Pa+ LZD (300mg)Experimental9 wks. of BDQ +Pa + LZD (600mg) followed by 17 wks. of BDQ +Pa+ LZD (300mg) Bedaquiline (available as 100 mg tablets) Bedaquiline will be administered as four 100 mg tablets (400 mg) by mouth once a day for 2 weeks, followed by two 100 mg tablets (200 mg) by mouth three times a week for 24 weeks. Linezolid: (available as 600 mg tablets) - Linezolid will be administered as one 600 mg tablet once daily in IP of Arm 2 and ½ tablet of 600 mg once daily in CP of Arm 2 . Pretomanid: (Available as 200 mg tablets): Pretomanid is administered as one tablet once a day for 26 weeks along with Bedaquiline and Linezolid.
Receives: Drug: Linezolid; Drug: Bedaquiline; Drug: Pretomanid
Arm 3 -13 weeks. of BDQ +Pa + LZD (600mg) followed by 13 wks. of BDQ +Pa+ LZD (300mg)Experimental13 wks. of BDQ +Pa + LZD (600mg) followed by 13 wks. of BDQ +Pa+ LZD (300mg) Bedaquiline (available as 100 mg tablets) Bedaquiline will be administered as four 100 mg tablets (400 mg) by mouth once a day for 2 weeks, followed by two 100 mg tablets (200 mg) by mouth three times a week for 24 weeks. Linezolid: (available as 600 mg tablets) - Linezolid will be administered as one 600 mg tablet once daily in IP of Arm 3 and ½ tablet of 600 mg once daily in CP of Arm 3. Pretomanid: (Available as 200 mg tablets): Pretomanid is administered as one tablet once a day for 26 weeks along with Bedaquiline and Linezolid.
Receives: Drug: Linezolid; Drug: Bedaquiline; Drug: Pretomanid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Sustained Treatment success

    Sustained Treatment success at 12 months after successful TB treatment, who is alive and free of TB. Successful TB treatment includes Cure and Treatment Completed.

    Measured: 12 months after successful TB treatment

Secondary outcomes (4)

  1. Proportion of serious adverse events

    1. Proportion of serious adverse events occurring among patients in the study during the treatment and follow-up period

    Measured: treatment and follow-up period - 18 months

  2. proportion of patients died

    Died due to any cause during treatment

    Measured: treatment and follow-up period - 18 months

  3. proportion of patients with Treatment Failure

    Treatment terminated or need for permanent regimen change to a new regimen or treatment strategy because of lack of sputum culture conversion , • bacteriological reversion , clinical or radiological worsening

    Measured: treatment and follow-up period - 18 months

  4. proportion of patients with Lost-to-follow up

    After treatment initiation, treatment was interrupted continuously for 30-days

    Measured: treatment and follow-up period - 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2021
  2. Study start7 Oct 2021
  3. Primary completion31 Dec 2024 (estimated)
  4. Study completion31 Dec 2024 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Pragmatic Clinical Trial
Masking
None (open label)
Enrolment
400 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05040126
Sponsor's protocol ID
2021 004
Acronym
mBPaL
Status last verified
Dec 2023
First submitted
18 Aug 2021
Last updated
3 Jan 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Padmapriyadarsini C, Devaleenal B, Ponnuraja C, Ramraj B, Singla R, Parmar M, Mattoo S, Mandal S. Randomised trial to evaluate the effectiveness and safety of varying doses of linezolid with bedaquiline and pretomanid in adults with pre-extensively drug-resistant or treatment intolerant/non-responsive multidrug-resistant pulmonary tuberculosis: study protocol. BMJ Open. 2022 Aug 29;12(8):e058606. doi: 10.1136/bmjopen-2021-058606.

    PubMed 36038181

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Linezolid, Bedaquiline and Pretomanid in people with Pre-Extensively Drug-Resistant Pulmonary TB and Treatment Intolerant Multidrug-Resistant Pulmonary TB, run by Tuberculosis Research Centre, India at 1 site in India.

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 8 inclusion and 19 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: status not confirmed, as of the sponsor's last update on 3 Jan 2024. 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 India. 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 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?

Results are not available in the source record.

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?

Sustained Treatment success (time frame: 12 months after successful TB treatment). 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 NCT05040126, 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 3 Jan 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in