AzTrials
AzTrials

Pulmonary TuberculosisPhase 2NCT05896930

Study to Evaluate EBA, Safety and Tolerability of Carbapenems in Adults With Pulmonary Tuberculosis

A Phase 2 study testing Meropenem 6g IV over 6 hours, Ertapenem 1g IM and Meropenem 3g IV in people with Pulmonary Tuberculosis, run by TASK Applied Science at 1 site in South Africa.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The goal of this single-center, open-labelled, clinical trial in two groups aims to proof that a specific group of antibiotics (carbapenems) can be used to treat pulmonary tuberculosis if it is combined with another antibiotic (amoxicillin/clavulanate). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Pulmonary Tuberculosis
What is being tested?
Meropenem 6g IV over 6 hours, Ertapenem 1g IM and Meropenem 3g IV
Could I receive a placebo?
No, everyone receives an active treatment
How many people
134 participants
Where
1 siteSouth Africa
Study dates
9 Nov 2017to 4 Jan 2021
Phase
Phase 2
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

  • Provide written, informed consent prior to all trial-related procedures including HIV testing.
  • Male or female, aged between 18 and 65 years, inclusive.
  • Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
  • Newly diagnosed, previously untreated, rifampicin-susceptible pulmonary TB.
  • A chest X-ray picture which in the opinion of the Investigator is consistent with TB.
  • Sputum positive on direct microscopy for acid-fast bacilli on at least one sputum sample (at least 1+ on the IUATLD/WHO scale).
Show all 16Show fewer
  • Ability to produce an adequate volume of sputum as estimated from an overnight sputum collection sample (estimated 10 ml or more).
  • Be of non-childbearing potential or using effective methods of birth control, as defined below:
  • Non-childbearing potential:
  • Participant - not heterosexually active or practicing sexual abstinence; or
  • Female participant/sexual partner - bilateral oophorectomy, bilateral tubal ligation and/or hysterectomy or has been postmenopausal with a history of no menses for at least 12 consecutive months; or
  • Male participant/sexual partner - vasectomised or has had a bilateral orchidectomy minimally three month prior to screening;
  • Effective birth control methods:
  • Double barrier method which can include a male condom, diaphragm, cervical cap, or female condom (male and female condoms should not be used together); or
  • Barrier method combined with hormone-based contraceptives or an intra-uterine device for the female partner; and are willing to continue practicing birth control methods throughout participation in the study until Visit 19 (day 28).
  • (Note: hormone-based contraception alone may not be reliable when taking IP; therefore, hormone-based contraceptives alone cannot be used by female participants to prevent pregnancy).

Who cannot join

  • Evidence of clinically significant conditions or findings, other than the indication being studied, particularly epilepsy, that might compromise safety or the interpretation of trial endpoints, per discretion of the Investigator.
  • Poor general condition where any delay in treatment cannot be tolerated per discretion of the Investigator.
  • A history of TB less than 3 years ago.
  • Clinically significant evidence of extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis), as judged by the Investigator.
  • History of allergy to any of the trial IP/s or related substances i.e. β-lactams and penicillin, as confirmed by the clinical judgement of the Investigator.
  • Known or suspected, current or history of within the past 2 years, alcohol or drug abuse, that is, in the opinion of the Investigator, sufficient to compromise the safety or cooperation of the participant.
Show all 22Show fewer
  • HIV infected participants.
  • Having participated in other clinical studies with investigational agents within 8 weeks prior to trial start.
  • Female participant who is pregnant, breast-feeding, or planning to conceive a child within the anticipated period of participating in the trial. Male participant planning to conceive a child within the anticipated period of participating in the trial.
  • Subjects with diabetes (Type 1 or 2), point of care HbA1c above 6.5, or random glucose over 11.1 mmol/L.
  • Hypersensitivity to local anaesthesia of amide type.
  • Treatment received with any drug active against MTB (including but not limited to isoniazid, ethambutol, amikacin, cycloserine, fluoroquinolones, rifabutin, rifampicin, streptomycin, kanamycin, para-aminosalicylic acid, rifapentine, pyrazinamide, thioacetazone, capreomycin, thioamides, metronidazole), or with immunosuppressive medications such as TNF-alpha inhibitors or systemic or inhaled corticosteroids, within 2 weeks prior to screening
  • Participants with the following toxicities at screening as defined by the enhanced CTCEA toxicity table
  • creatinine grade 2 or greater (>1.5 times upper limit of normal [ULN]);
  • haemoglobin <7.5 g/dL;
  • platelets grade 2 or greater (under 50x109 cells/L);
  • serum potassium grade 2 or greater (<3.0 mEq/L);
  • aspartate aminotransferase (AST) grade 3 (≥3.0 x ULN) to be excluded;
  • alanine aminotransferase (ALT) grade 3 (≥3.0 x ULN) to be excluded;
  • APTT grade 3
  • INR grade 3
  • Total white cell count grade 3

Trial locations and contacts

1 site in 1 country.

South Africa1 site

  • TASK Clinical Research Centre

    Cape Town, Western Cape, 7530

Other trials in South Africa

About this study

Official title: Phase 2 Trial to Evaluate the Early EBA, Safety and Tolerability of Amoxicillin/Clavulanate With or Without Meropenem, Ertapenem or Rifampicin in Adults With Newly Diagnosed, Smear-Positive Rifampicin-Susceptible Pulmonary Tuberculosis

The goal of this single-center, open-labelled, clinical trial in two groups aims to proof that a specific group of antibiotics (carbapenems) can be used to treat pulmonary tuberculosis if it is combined with another antibiotic (amoxicillin/clavulanate). A total of 113 male or female participants (8 groups and 9 treatment regimens as group 8 was split into 2 groups of 4 participants receiving Rifafour e-275), aged between 18 and 65 years (inclusive), with newly diagnosed, smear-positive, pulmonary TB.

Read the detailed description

The overall objective of this study is to evaluate the 2-week bactericidal activity and pharmacokinetics of the following beta-lactam containing combinations with the aim to select the most active and implementable solution to be incorporated into a drug-resistant TB combination regimen:

  • Once or twice daily meropenem administered intravenously in combination with once or twice daily oral amoxicillin/clavulanic acid;
  • Once daily ertapenem administered intravenously and intramuscularly in combination with twice daily oral amoxicillin/clavulanic acid;
  • Twice daily oral amoxicillin/clavulanic acid;
  • Once daily rifampicin administered orally at highest currently established dosage of 35mg/kg in combination with twice daily oral amoxicillin/clavulanic acid.

A single-center, open-labeled, clinical trial in two groups. The treatments are:

Group 1:

  1. Meropenem 6g intravenously once daily; plus amoxicillin/CA 2 x 1000mg/62.5mg orally 12-hourly on days 1-14.
  2. Ertapenem 1g intramuscularly once daily; plus amoxicillin/CA 2 x 1000mg/62.5mg orally 12-hourly on days 1-14. Group 2:
  3. Meropenem 3g intravenously twice daily; plus amoxicillin/CA 2 x 1000mg/62.5mg orally 12-hourly on days 1-14.
  4. Ertapenem 1g intravenously once daily; plus amoxicillin/CA 2 x 1000mg/62.5mg orally 12-hourly on days 1-14.
  5. Amoxicillin/CA 2 x 1000mg/62.5mg orally 12-hourly on days 1-14.
  6. Rifampicin 35 mg/kg once daily; plus amoxicillin/CA 2 x 1000mg/62.5mg orally 12-hourly on days 1-14.
  7. Meropenem 6g OR meropenem 4g intravenously once daily; plus amoxicillin/CA 2 x 1000mg/62.5mg orally once daily on days 1-14.

A total of 4 participants per group will receive standard first line TB treatment as per the South African TB guidelines (Rifafour e-275) and is included as a control for the EBA quantitative mycobacteriology and to evaluate whether HRZE gives similar EBA results to that demonstrated in prior studies with this combination. The mycobacteriology laboratory will remain blinded until closure of the EBA results. Enrollment into group 1 will be completed before enrollment into group 2 will start. After completion of enrollment into group 1, there will be an interim analysis while enrollment into group 2 is ongoing.

Being tested
Meropenem 6g IV over 6 hours, Ertapenem 1g IM, Meropenem 3g IV, Ertapenem 1g IV, Amoxicillin/CA twice daily
Keywords
EBA, Intravenous Meropenem, Newly Diagnosed, Smear-Positive, Rifampicin-Susceptible, Pulmonary Tuberculosis
Medical subject headings
Tuberculosis, Pulmonary

What participants receive

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

  • Meropenem 6g IV over 6 hoursDrug

    Meropenem 6g intravenously over 6 hours once daily on days 1-14.

  • Ertapenem 1g IMDrug

    Ertapenem 1g intramuscularly once daily on days 1-14.

  • Meropenem 3g IVDrug

    Meropenem 3g intravenously twice daily over 60 minutes on days 1-14.

  • Ertapenem 1g IVDrug

    Ertapenem 1g intravenously once daily on days 1-14.

  • Amoxicillin/CA twice dailyDrug

    Amoxicillin/CA 2 tablets x 1000mg/62.5mg orally 12-hourly on days 1-14.

  • Rifampicin 35 mg/kgDrug

    Rifampicin 35 mg/kg once daily on days 1-14.

  • Meropenem 6g IV over 60 minutesDrug

    Meropenem 6g intravenously once daily over 60 minutes on days 1-14.

  • Rifafour e-275Drug

    Rifafour e-275 will be supplied as fixed dose combination tablets and administered orally once daily for 14 days as The daily dose is dependent on the participants' weight as follows: 40 - 54kg: 3 tablets; 55 - 70kg: 4 tablets; 71kg and over: 5 tablets.

  • Meropenem 4g IVDrug

    Meropenem 4g intravenously once daily over 60 minutes on days 1-14.

  • Amoxicillin/CA once dailyDrug

    Amoxicillin/CA 2 tablets x 1000mg/62.5mg orally once daily on days 1-14.

Study groups in NCT05896930
Study groupRoleWhat they receive
Group 1 Arm 1ExperimentalMeropenem 6g IV over 6 hours plus amoxicillin/CA
Receives: Drug: Meropenem 6g IV over 6 hours; Drug: Amoxicillin/CA twice daily
Group 1 Arm 2ExperimentalErtapenem 1g IM plus amoxicillin/CA
Receives: Drug: Ertapenem 1g IM; Drug: Amoxicillin/CA twice daily
Group 2 Arm 1ExperimentalMeropenem 3g over 1 hour twice daily plus amoxicillin/CA
Receives: Drug: Meropenem 3g IV; Drug: Amoxicillin/CA twice daily
Group 2 Arm 2ExperimentalErtapenem 1g IV plus amoxicillin/CA
Receives: Drug: Ertapenem 1g IV; Drug: Amoxicillin/CA twice daily
Group 2 Arm 3ExperimentalAmoxicillin; CA
Receives: Drug: Amoxicillin/CA twice daily
Group 2 Arm 4ExperimentalRifampicin 35mg/kg plus amoxicillin/CA
Receives: Drug: Amoxicillin/CA twice daily; Drug: Rifampicin 35 mg/kg
Group 2 Arm 5ExperimentalMeropenem 6g or 4g IV over 60 minutes plus amoxicillin/CA
Receives: Drug: Meropenem 6g IV over 60 minutes; Drug: Meropenem 4g IV; Drug: Amoxicillin/CA once daily
Group 1Active comparatorRifafour e-275
Receives: Drug: Rifafour e-275

What is being measured

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

  1. Early bactericidal activity by change in logCFU over 14 days

    The EBACFU(0-14) as determined by the rate of change in logCFU (colony forming units) per ml sputum over the period Day 0 to Day 14 which will be summarised and described with a statistical model as an estimated average decrease per day for patients in each group.

    Measured: 14 days

  2. Early bactericidal activity by change in time-to-positivity over 14 days

    The EBATTP(0-14) as determined by the percentage rate of change in TTP (time to positivity) per ml sputum over the period Day 0 to Day 14, which will be summarised and described with a statistical model as an estimated average increase per day for patients in each group.

    Measured: 14 days

Secondary outcomes (1)

  1. Early bactericidal activity by change in logCFU and TTP per ml over 0-2 days, 0-7 days, and 2-14 days

    Drug activity with CFU or TTP over different treatment periods such as 0-2 days, 0-7 days, and 2-14 days as indicated, for cross-comparison with other published data.

    Measured: 0-2 days, 0-7 days, 2-14 days

Timeline

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

  1. First posted9 Jun 2023
  2. Study start9 Nov 2017
  3. Primary completion4 Jan 2021
  4. Study completion4 Jan 2021

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 2
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Model description
This study will be a standard 14 day EBA design incorporating 2 groups with parallel treatment arms. This design allows comparison of the results of this study with similar prior studies of treatments for TB. No placebo treatment is included in this study - all participants will be given either active study treatment or Rifafour e275® control. The planned sample size is15 participants per treatment group.
Masking
None (open label)
Enrolment
134 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05896930
Sponsor's protocol ID
TASK 003
Status last verified
May 2023
First submitted
11 Apr 2023
Last updated
9 Jun 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Meropenem 6g IV over 6 hours, Ertapenem 1g IM and Meropenem 3g IV in people with Pulmonary Tuberculosis, run by TASK Applied Science at 1 site in South Africa.

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 16 inclusion and 22 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 9 Jun 2023. 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 South Africa. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Early bactericidal activity by change in logCFU over 14 days (time frame: 14 days). The study lists 2 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 NCT05896930.

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 9 Jun 2023.

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

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in