Disseminated TuberculosisPhase 3NEW-STRAT TBNCT04951986
Testing New Strategies for Patients Hospitalised With HIV-associated Disseminated Tuberculosis
A Phase 3 study testing Rifampin, Levofloxacin and Rifampicin, Pyrazinamide, Ethambutol and Isoniazid in people with Disseminated Tuberculosis and HIV, run by University of Cape Town at 2 sites in South Africa.
Trial summary
The New Strat-TB trial is a superiority Phase III randomised control clinical trial with a 2X2 factorial design. The main aim of the study is to assess the efficacy and safety of high dose rifampicin and levofloxacin for 14 days in addition to standard TB therapy with or without steroids among adults hospitalized with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Disseminated Tuberculosis, HIV
- What is being tested?
- Rifampin, Levofloxacin and Rifampicin, Pyrazinamide, Ethambutol and Isoniazid
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 732 participants
- Where
- 2 sitesSouth Africa
- Study dates
- 11 Aug 2021to Mar 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Aged >18
- HIV infection
- Disseminated TB confirmed by one or more of the following tests being positive
- Lysed blood Xpert Ultra positive for MTB
- Concentrated urine Xpert Ultra positive for MTB
- Urine Alere LAM positive
- Hospital clinical team made decision to initiate TB treatment
Who cannot join
- Pregnant or breastfeeding
- Active or recent SARS-CoV-2 infection
- TB treatment within the last 1 month or more than 2 doses of TB treatment
- Rifampicin resistance
- Neurological TB
- Receiving corticosteroids or other immunosuppressive therapy
Show all 12Show fewer
- ALT >120 IU/L or total bilirubin >34 μmol/L
- Plasma CrAg positive or cryptococcal meningitis
- Current malignancy requiring active treatment (including any Kaposi sarcoma lesions)
- Patients established on ART with Protease Inhibitor based regimen who cannot be switched to a dolutegravir based regimen
- Diabetic ketoacidosis or Hyperosmolar Non-ketotic acidosis
- Any condition in the opinion of the investigator for which participation would increase risk to the patient
Trial locations and contacts
2 sites in 1 country.
South Africa2 sites
Khayelitsha Hospital, c/o Steve Biko and Walter Sisulu Drives, Khayelitsha
Cape Town, Western Cape, 7784
Mitchells Plain Hospital, Mitchells PLain
Cape Town, Western Cape, 7785
About this study
The New Strat-TB trial is a superiority Phase III randomised control clinical trial with a 2X2 factorial design. The main aim of the study is to assess the efficacy and safety of high dose rifampicin and levofloxacin for 14 days in addition to standard TB therapy with or without steroids among adults hospitalized with HIV-associated disseminated tuberculosis.
The investigators hypothesize that intensified treatment with increased rifampicin doses at 35 mg/kg plus levofloxacin will more rapidly reduce the mycobacterial load. The investigators also hypothesize that steroids will have an immune-modulatory effect and dampen the activation of the innate immune system. The investigators hypothesize that these two strategies will lead to improved survival in patients hospitalized with HIV-associated disseminated tuberculosis.
Read the detailed description
Primary efficacy endpoint:
All-cause mortality at 12 weeks
Secondary efficacy endpoint:
All-cause mortality at 2 and 24 weeks
Safety and tolerability endpoints:
- Occurrence of hepatotoxicity using the American Thoracic Society (ATS) hepatotoxicity criteria: Alanine aminotransferase (ALT) elevation of more than three times the upper limit of normal (ULN) in the presence of hepatitis symptoms and/or jaundice or five times the upper limit of normal in the absence of symptoms.
- Corticosteroid-associated adverse events, classified by severity and relation to study drug and will be reported if these develop within 4 weeks of enrolment. These will include new hypertension, new poor blood pressure control in a known hypertensive, hyperglycaemia, hypomania, mania, depression, acne, gastritis symptoms, upper gastrointestinal bleeding, and avascular bone necrosis.
- Laboratory safety data (Grade 3 and 4 abnormalities using the ACTG grading system): liver function tests (alanine and aspartate aminotransferase[ALT, AST], gammaglutamyl transferase [GGT], alkaline phosphatase [ALP], International Normalized Ratio [INR], conjugated and total bilirubin [CBR, TBR]), glucose, full blood counts (including white cell, neutrophil and platelet counts plus haemoglobin) and electrolytes (sodium, potassium) and creatinine.
- Occurrence of other opportunistic infections (AIDS-related, bacterial, fungal and viral) and malignancies (Kaposi's sarcoma) up to 12 weeks.
- Occurrence of paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in patients starting antiretroviral therapy up to 12 weeks.
- All grade 3 and 4 clinical adverse events (using the ACTG grading system)
- Serious adverse events
- Adverse events requiring study drug interruption and or withdrawal
- Adverse drug reactions attributed to study drug
Follow-up:
Participants will be followed up daily while admitted to hospital for assessment of adverse events. Safety and routine blood tests will be done on day 2, 4, 7, 14 and 28. Further visits will be on week 12 and 24.
Data monitoring:
The trial will be monitored by an independent Data and Safety Monitoring Board (DSMB) comprising 4 independent researchers and an independent statistician. If there is evidence of harm related to study medication or trial conduct the DSMB may advise the sponsor that trial enrolment should be stopped.
Clinical trial site:
Mitchells Plain Hospital and Khayelitsha Hospital
- Conditions
- Disseminated Tuberculosis, HIV
- Being tested
- Rifampin, Levofloxacin, Rifampicin, Pyrazinamide, Ethambutol and Isoniazid, Prednisone, Placebo
- Keywords
- HIV, High dose rifampicin, Fluoroquinolones, Glucocorticoids, Antiretroviral therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RifampinDrug
Also called rifampicin, Rifadin, Rimactane
Rifampicin up to 35 mg/kg/day for 14 days
LevofloxacinDrug
Levofloxacin 750mg daily (for weight <50kg) or 1 g daily (for weight >50 kg) daily for 14 days
Rifampicin, Pyrazinamide, Ethambutol and IsoniazidDrug
Also called Rifafour
Rifampicin 10 mg/kg; Isoniazid 5 mg/kg; Pyrazinamide 15 mg/kg; Ethambutol15 mg/kg in fixed dose combination administered per weight band. Standard of care control arm
PrednisoneDrug
Also called Trolic
Prednisone 1.5mg/kg/day for 14 days
PlaceboDrug
Placebo identical to Prednisone
| Study group | Role | What they receive |
|---|---|---|
| High dose Rifampicin plus Levofloxacin | Experimental | Standard TB treatment plus additional Rifampicin 35 mg/kg/day PLUS Levofloxacin for 14 days Receives: Drug: Rifampin; Drug: Levofloxacin; Drug: Rifampicin, Pyrazinamide, Ethambutol and Isoniazid |
| Prednisone | Experimental | Prednisone 1.5 mg/kg for 14 days Receives: Drug: Prednisone |
| Standard TB treatment | Active comparator | High dose rifampicin/levofloxacin comparator Receives: Drug: Rifampicin, Pyrazinamide, Ethambutol and Isoniazid |
| Placebo | Placebo comparator | Prednisone comparator Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause mortality
Measured: 12 weeks
Secondary outcomes (2)
In-hospital mortality during index admission
Measured: 7 days
All-cause mortality
Measured: 2 and 24 weeks respectively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2021
- Study start11 Aug 2021
- Primary completion15 Dec 2025
- Study completionMar 2026 (estimated)
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 Disseminated TuberculosisStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- First intervention (open label): a) Experimental arm: Standard first-line anti-tuberculosis therapy plus additional rifampicin to reach 35mg/kg/day for 14 days plus levofloxacin 750mg/day for weight \<50kg and 1g/day for weight \>50kg for 14 days b) Control arm: Standard TB therapy containing rifampicin 10mg/kg for 14 days (standard of care) After 14 days both study arms will continue standard TB therapy with rifampicin at 10mg/kg to complete 2 months of intensive phase in total. This will be followed by standard continuation phase TB therapy. 2\. Second intervention (double-blind): 1. Experimental arm: Prednisone 1.5mg/kg per day for 14 days 2. Control arm: Identical placebo for 14 days
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 732 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cape Town
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Charlotte Schutz, University of Cape Town
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04951986
- Sponsor's protocol ID
- HREC REF: 001/2021
- Acronym
- NEW-STRAT TB
- Status last verified
- Dec 2025
- First submitted
- 30 Jun 2021
- Last updated
- 6 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be shared on request, after discussion with ethics committee
Publications
Namale PE, Boloko L, Vermeulen M, Haigh KA, Bagula F, Maseko A, Sossen B, Lee-Jones S, Msomi Y, McIlleron H, Mnguni AT, Crede T, Szymanski P, Naude J, Ebrahim S, Vallie Y, Moosa MS, Bandeker I, Hoosain S, Nicol MP, Samodien N, Centner C, Dowling W, Denti P, Gumedze F, Little F, Parker A, Price B, Schietekat D, Simmons B, Hill A, Wilkinson RJ, Oliphant I, Hlungulu S, Apolisi I, Toleni M, Asare Z, Mpalali MK, Boshoff E, Prinsloo D, Lakay F, Bekiswa A, Jackson A, Barnes A, Johnson R, Wasserman S, Maartens G, Barr D, Schutz C, Meintjes G. Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial. Trials. 2024 May 8;25(1):311. doi: 10.1186/s13063-024-08119-4.
PubMed 38720383
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Testing New Strategies for Patients Hospitalised With HIV-associated Disseminated Tuberculosis
- ClinicalTrials.gov ID
- NCT04951986
- Acronym / sponsor ID
- NEW-STRAT TB / HREC REF: 001/2021
- Conditions
- Disseminated Tuberculosis, HIV
- Keywords
- HIV, High dose rifampicin, Fluoroquinolones, Glucocorticoids, Antiretroviral therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 732 participants (estimated)
- Lead sponsor
- University of Cape TownUniversity, hospital or other
- Study start
- 11 Aug 2021 (actual)
- Primary completion
- 15 Dec 2025 (actual)
- Study completion
- Mar 2026 (estimated)
- First posted
- 7 Jul 2021 (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.
The New Strat-TB trial is a superiority Phase III randomised control clinical trial with a 2X2 factorial design. The main aim of the study is to assess the efficacy and safety of high dose rifampicin and levofloxacin for 14 days in addition to standard TB therapy with or without steroids among adults hospitalized with HIV-associated disseminated tuberculosis.
The investigators hypothesize that intensified treatment with increased rifampicin doses at 35 mg/kg plus levofloxacin will more rapidly reduce the mycobacterial load. The investigators also hypothesize that steroids will have an immune-modulatory effect and dampen the activation of the innate immune system. The investigators hypothesize that these two strategies will lead to improved survival in patients hospitalized with HIV-associated disseminated tuberculosis.
Detailed description
Primary efficacy endpoint:
All-cause mortality at 12 weeks
Secondary efficacy endpoint:
All-cause mortality at 2 and 24 weeks
Safety and tolerability endpoints:
- Occurrence of hepatotoxicity using the American Thoracic Society (ATS) hepatotoxicity criteria: Alanine aminotransferase (ALT) elevation of more than three times the upper limit of normal (ULN) in the presence of hepatitis symptoms and/or jaundice or five times the upper limit of normal in the absence of symptoms.
- Corticosteroid-associated adverse events, classified by severity and relation to study drug and will be reported if these develop within 4 weeks of enrolment. These will include new hypertension, new poor blood pressure control in a known hypertensive, hyperglycaemia, hypomania, mania, depression, acne, gastritis symptoms, upper gastrointestinal bleeding, and avascular bone necrosis.
- Laboratory safety data (Grade 3 and 4 abnormalities using the ACTG grading system): liver function tests (alanine and aspartate aminotransferase[ALT, AST], gammaglutamyl transferase [GGT], alkaline phosphatase [ALP], International Normalized Ratio [INR], conjugated and total bilirubin [CBR, TBR]), glucose, full blood counts (including white cell, neutrophil and platelet counts plus haemoglobin) and electrolytes (sodium, potassium) and creatinine.
- Occurrence of other opportunistic infections (AIDS-related, bacterial, fungal and viral) and malignancies (Kaposi's sarcoma) up to 12 weeks.
- Occurrence of paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in patients starting antiretroviral therapy up to 12 weeks.
- All grade 3 and 4 clinical adverse events (using the ACTG grading system)
- Serious adverse events
- Adverse events requiring study drug interruption and or withdrawal
- Adverse drug reactions attributed to study drug
Follow-up:
Participants will be followed up daily while admitted to hospital for assessment of adverse events. Safety and routine blood tests will be done on day 2, 4, 7, 14 and 28. Further visits will be on week 12 and 24.
Data monitoring:
The trial will be monitored by an independent Data and Safety Monitoring Board (DSMB) comprising 4 independent researchers and an independent statistician. If there is evidence of harm related to study medication or trial conduct the DSMB may advise the sponsor that trial enrolment should be stopped.
Clinical trial site:
Mitchells Plain Hospital and Khayelitsha Hospital
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- First intervention (open label): a) Experimental arm: Standard first-line anti-tuberculosis therapy plus additional rifampicin to reach 35mg/kg/day for 14 days plus levofloxacin 750mg/day for weight <50kg and 1g/day for weight >50kg for 14 days b) Control arm: Standard TB therapy containing rifampicin 10mg/kg for 14 days (standard of care) After 14 days both study arms will continue standard TB therapy with rifampicin at 10mg/kg to complete 2 months of intensive phase in total. This will be followed by standard continuation phase TB therapy. 2. Second intervention (double-blind): 1. Experimental arm: Prednisone 1.5mg/kg per day for 14 days 2. Control arm: Identical placebo for 14 days
| Arm | Type | Receives |
|---|---|---|
| High dose Rifampicin plus Levofloxacin | Experimental | Drug: Rifampin, Drug: Levofloxacin, Drug: Rifampicin, Pyrazinamide, Ethambutol and IsoniazidStandard TB treatment plus additional Rifampicin 35 mg/kg/day PLUS Levofloxacin for 14 days |
| Prednisone | Experimental | Drug: PrednisonePrednisone 1.5 mg/kg for 14 days |
| Standard TB treatment | Active comparator | Drug: Rifampicin, Pyrazinamide, Ethambutol and IsoniazidHigh dose rifampicin/levofloxacin comparator |
| Placebo | Placebo comparator | Drug: PlaceboPrednisone comparator |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Aged >18
- HIV infection
- Disseminated TB confirmed by one or more of the following tests being positive
- Hospital clinical team made decision to initiate TB treatment
Key exclusion criteria (12 listed)
- Pregnant or breastfeeding
- Active or recent SARS-CoV-2 infection
- TB treatment within the last 1 month or more than 2 doses of TB treatment
- Rifampicin resistance
- Neurological TB
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 |
|---|---|---|
| RifampinAlso: rifampicin, Rifadin, RimactaneRifampicin up to 35 mg/kg/day for 14 days | Drug | High dose Rifampicin plus Levofloxacin |
| LevofloxacinLevofloxacin 750mg daily (for weight <50kg) or 1 g daily (for weight >50 kg) daily for 14 days | Drug | High dose Rifampicin plus Levofloxacin |
| Rifampicin, Pyrazinamide, Ethambutol and IsoniazidAlso: RifafourRifampicin 10 mg/kg; Isoniazid 5 mg/kg; Pyrazinamide 15 mg/kg; Ethambutol15 mg/kg in fixed dose combination administered per weight band. Standard of care control arm | Drug | High dose Rifampicin plus Levofloxacin, Standard TB treatment |
| PrednisoneAlso: TrolicPrednisone 1.5mg/kg/day for 14 days | Drug | Prednisone |
| PlaceboPlacebo identical to Prednisone | Drug | Placebo |
Primary outcome
All-cause mortality
Time frame: 12 weeks
2 secondary outcomes
In-hospital mortality during index admission
Time frame: 7 days
All-cause mortality
Time frame: 2 and 24 weeks respectively
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2026.
- Derived from this study: PubMed 38720383Namale PE, Boloko L, Vermeulen M, Haigh KA, Bagula F, Maseko A, Sossen B, Lee-Jones S, Msomi Y, McIlleron H, Mnguni AT, Crede T, Szymanski P, Naude J, Ebrahim S, Vallie Y, Moosa MS, Bandeker I, Hoosain S, Nicol MP, Samodien N, Centner C, Dowling W, Denti P, Gumedze F, Little F, Parker A, Price B, Schietekat D, Simmons B, Hill A, Wilkinson RJ, Oliphant I, Hlungulu S, Apolisi I, Toleni M, Asare Z, Mpalali MK, Boshoff E, Prinsloo D, Lakay F, Bekiswa A, Jackson A, Barnes A, Johnson R, Wasserman S, Maartens G, Barr D, Schutz C, Meintjes G. Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial. Trials. 2024 May 8;25(1):311. doi: 10.1186/s13063-024-08119-4.
- Individual participant dataSharing planned: Yes. IPD will be shared on request, after discussion with ethics committee
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rifampin, Levofloxacin and Rifampicin, Pyrazinamide, Ethambutol and Isoniazid in people with Disseminated Tuberculosis and HIV, run by University of Cape Town at 2 sites 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 7 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 6 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. 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 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?
This study is still under way. Results are not available in the source record yet.
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?
All-cause mortality (time frame: 12 weeks). 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 NCT04951986, 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 6 Jan 2026.