TuberculosisPhase 3ATLASNCT04618198
Early Empiric Anti-Mycobacterium Tuberculosis Therapy for Sepsis in Sub-Saharan Africa
A Phase 3 study testing Immediate anti-TB therapy and Sepsis-specific dose anti-TB therapy in people with Tuberculosis and HIV I Infection, run by University of Virginia at 2 sites in 2 countries.
Trial summary
In sub-Saharan Africa, tuberculosis (TB) is the etiology of 25-50% of bloodstream infections (BSIs) and the leading cause of sepsis among people living with HIV. TB BSI is associated with 20-50% mortality, and 20-25% of deaths occur within five days of admission. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, HIV I Infection, Sepsis
- What is being tested?
- Immediate anti-TB therapy and Sepsis-specific dose anti-TB therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 437 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 5 Jan 2022to 20 May 2025
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female aged ≥18 years living with HIV
- Admitted to hospital with 1) clinical concern for infection; 2) ≥2 qSOFA score criteria (Glasgow Coma Scale score <15, a respiratory rate ≥22, or a systolic blood pressure ≤90 mmHg or a mean arterial pressure of ≤65 mmHg)
- Resident within a pre-defined geographic area to ensure TB clinic follow-up
- For females of reproductive potential: use of highly effective contraception through 28 days
Who cannot join
- Known active TB or receiving anti-TB therapy
- Pregnancy or lactation. Women will undergo urine pregnancy screening. Pregnant women will be excluded due to the possible toxicity and teratogenicity of high dose rifampin and isoniazid included in anti-TB therapy as well as possible teratogenicity of dolutegravir which is recommended as first-line antiretroviral therapy in this study.
- Known allergic reactions to the components of the anti-TB therapy
- Treatment with another investigational drug or other intervention within one month
- Known liver disease
- Alcohol use > 14 standardized drinks per week and/or > 4 drinks per day for men and >7 standardized drinks per week and/or >3 drinks per day for women, defined as 14 grams of ethanol, as found in example 5 ounces of wine, 12 ounces of beer, or 1.5 ounces of 80 proof spirits
- Positive serum cryptococcal antigen test
- Current treatment with a drug known to have significant interaction with anti-TB therapy
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Randomized Clinical Trial of Early Empiric Anti-Mycobacterium Tuberculosis Therapy for Sepsis in Sub-Saharan Africa
In sub-Saharan Africa, tuberculosis (TB) is the etiology of 25-50% of bloodstream infections (BSIs) and the leading cause of sepsis among people living with HIV. TB BSI is associated with 20-50% mortality, and 20-25% of deaths occur within five days of admission. TB BSI is difficult to identify clinically and microbiologically. Given that the high prevalence of TB BSI is under-recognized, most patients with sepsis in sub-Saharan Africa do not receive early anti-TB therapy. The hypothesis of this study is that immediate and optimally dosed anti-TB therapy will improve 28 day mortality in patients with sepsis in Uganda and Tanzania. Therefore, the overall goal is to conduct a phase 3 multi-site open label 2x2 factorial clinical trial of 1) empiric immediate initiation of anti-TB therapy plus standard care compared to diagnosis dependent anti-TB therapy plus standard care and 2) sepsis-specific dose anti-TB therapy plus standard care compared to conventional WHO weight-based dose anti-TB therapy plus standard care for the treatment of sepsis in people living with HIV admitted to our longstanding collaborative research sites at either the Mbarara Regional Referral Hospital in Mbarara, Uganda, or Kilimanjaro region hospitals in Moshi, Tanzania.
Read the detailed description
The primary objective of this clinical trial is to:
- To conduct a randomized 2x2 factorial clinical trial of 1) empiric immediate initiation of anti-TB therapy plus standard care vs diagnosis dependent anti-TB therapy plus standard care, 2) sepsis-specific anti-TB therapy plus standard care vs conventional WHO weight-based anti-TB therapy plus standard care for patients presenting with sepsis in Uganda and Tanzania.
1a) To determine if empiric immediate initiation of anti-TB therapy plus standard care improves 28 day mortality compared to diagnosis dependent anti-TB therapy plus standard care.
1b) To determine if sepsis-specific dose anti-TB therapy plus standard care improves 28 day mortality compared to conventional WHO weight-based anti-TB therapy plus standard care.
The secondary objectives include:
- To determine if empiric immediate initiation of anti-TB therapy plus standard care improves in-hospital mortality compared to diagnosis dependent anti-TB therapy plus standard care.
- To determine if sepsis-specific dose anti-TB therapy plus standard care improves in-hospital mortality compared to conventional WHO weight-based anti-TB therapy plus standard care.
- To determine if empiric immediate initiation of anti-TB therapy plus standard care improves 6 month mortality compared to diagnosis dependent anti-TB therapy plus standard care.
- To determine if sepsis-specific dose anti-TB therapy plus standard care improves 6 month mortality compared to conventional WHO weight-based anti-TB therapy plus standard care.
- To determine the safety of increased dose sepsis-specific anti-TB therapy for patients with sepsis
- To determine if early achievement of target serum drug concentrations of isoniazid and rifampin, measured at day-2 of TB treatment, associates with more rapid clinical improvement among patients with confirmed TB.
Participants will be men or women aged ≥18 years living with HIV in Tanzania or Uganda who are admitted to one of the study hospitals with sepsis, defined by a clinical concern for infection, a modified quick sepsis-related organ failure assessment (qSOFA) score ≥2 (Glasgow Coma Scale score <15, a respiratory rate ≥22, or a systolic blood pressure ≤90 mmHg or a mean arterial pressure of ≤65 mmHg). This is a multi-site trial at Kilimanjaro region hospitals in Tanzania (Kibong'oto Infectious Diseases Hospital and Kilimanjaro Christian Medical Centre) and Mbarara Regional Referral Hospital in Mbarara, Uganda. At both regional study sites, clinical trial infrastructure has been developed over multiple TB and non-TB related interventional studies supported by the NIH and other funders including EDCTP, WHO, MRC, and BMGF with associated regulatory standards. Furthermore, both regional hospital systems have large recruitment populations serving mid-sized cities where patients receive local care and as referral hospitals for those from more peripheral settings. The study population will be enrolled from the Emergency or inpatient wards. Admission numbers of eligible patients presenting with sepsis at each site allow for a conservative estimates of 100 patients per country per year to be well within attainment.
After enrollment, patients will be randomized to 1) empiric immediate initiation of anti-TB therapy plus standard care vs diagnosis dependent anti-TB therapy plus standard care and 2) conventional WHO recommended weight-based dose anti-TB therapy with rifampin, isoniazid, pyrazinamide, and ethambutol plus pyridoxine, plus standard therapy; or sepsis-specific dose anti-TB therapy with rifampin (~30mg/kg), isoniazid (~7.5mg/kg), pyrazinamide, and ethambutol plus pyridoxine, plus standard care.
Each individual participant will complete all participant follow-up at 6 months from enrollment.
- Conditions
- Tuberculosis, HIV I Infection, Sepsis
- Being tested
- Immediate anti-TB therapy, Sepsis-specific dose anti-TB therapy
- Medical subject headings
- Tuberculosis, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immediate anti-TB therapyOther
Study participants will receive immediate empiric anti-TB therapy
Sepsis-specific dose anti-TB therapyOther
Study participants will receive conventional WHO weight-based dose anti-TB therapy
| Study group | Role | What they receive |
|---|---|---|
| Diagnosis dependent / conventional dose anti-TB therapy | No intervention | Standard care per admitting team including ceftriaxone x 7 days If subsequent TB test positive, then WHO recommended weight-based anti-TB therapy x 28 days |
| Immediate anti-TB therapy/conventional dose anti-TB therapy | Experimental | Standard care per admitting team including ceftriaxone x 7 days plus immediate empiric WHO recommended weight-based dose anti-TB therapy x 28 days Receives: Other: Immediate anti-TB therapy |
| Diagnosis dependent/sepsis specific dose anti-TB therapy | Experimental | Standard care per admitting team including ceftriaxone x 7 days
If subsequent TB test positive, then sepsis specific dose anti-TB therapy x 28 days Receives: Other: Sepsis-specific dose anti-TB therapy |
| Immediate anti-TB therapy/sepsis specific dose anti-TB therapy | Experimental | Standard care per admitting team including ceftriaxone x 7 days plus immediate empiric sepsis specific dose anti-TB therapy x 28 days Receives: Other: Immediate anti-TB therapy; Other: Sepsis-specific dose anti-TB therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
28-day Mortality
number of participants with mortality
Measured: 28 days from enrollment
Secondary outcomes (13)
In-hospital Mortality
number of participants with mortality while admitted to the hospital
Measured: 28 days from enrollment
6-month Mortality
number of participants with mortality
Measured: 6 months from enrollment
Time to Death
time from enrollment to date of mortality
Measured: 6 months from enrollment
Duration of Hospitalization
time from enrollment to date of discharge from hospital, or death
Measured: 6 months from enrollment
Time to Anti-TB Therapy
Time to administration of anti-TB therapy. A value of 28 is assigned to those who did not receive anti-TB therapy.
Measured: 28 days from enrollment
Adverse Events
Number of participants with adverse events associated with the trial
Measured: 28 days from enrollment
Sepsis Etiology
pathogen identified in blood by molecular TAC platform or culture
Measured: baseline specimen collection
Time to Ambulation
time from enrollment to date of first ambulation, or death. Participants walking at start of study assigned 0, those who died prior to walking given a value of 28.
Measured: 28 days from enrollment
Time to Temperature Normalization
Time until participant has a normal temperature (above 36C and below 38C). Participants with normal temperature at baseline are assigned a value of 0.
Measured: 28 days from enrollment
Peak Drug Concentration Isoniazid
Serum isoniazid peak concentration (Cmax)
Measured: 2 days from enrollment
Peak Drug Concentration Rifampin
Serum rifampin peak concentration (Cmax)
Measured: 2 days from enrollment
Total Drug Exposure Isoniazid
Serum isoniazid total area under the concentration time curve (AUC)
Measured: 2 days from enrollment
Total Drug Exposure Rifampin
Serum total area under the concentration time curve (AUC)
Measured: 2 days from enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2020
- Study start5 Jan 2022
- Primary completion27 Dec 2024
- Study completion20 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- 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
- This is a phase 3, multi-site, open-label, randomized controlled clinical 2x2 factorial superiority trial of a) immediate initiation of anti-TB therapy and b) sepsis-specific dose anti-TB therapy for people living with HIV and presenting with sepsis to our regional study sites in Tanzania and Uganda.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 437 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Scott Heysell, MD, University of Virginia
- Investigators
- Christopher Moore, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04618198
- Sponsor's protocol ID
- 22611
- Other IDs
- U01AI150508-01A1
- Acronym
- ATLAS
- Status last verified
- Sep 2026
- First submitted
- 26 Oct 2020
- Last updated
- 9 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Moore CC, Jacob ST, Banura P, Zhang J, Stroup S, Boulware DR, Scheld WM, Houpt ER, Liu J. Etiology of Sepsis in Uganda Using a Quantitative Polymerase Chain Reaction-based TaqMan Array Card. Clin Infect Dis. 2019 Jan 7;68(2):266-272. doi: 10.1093/cid/ciy472.
PubMed 29868873Hazard RH, Kagina P, Kitayimbwa R, Male K, McShane M, Mubiru D, Welikhe E, Moore CC, Abdallah A. Effect of Empiric Anti-Mycobacterium tuberculosis Therapy on Survival Among Human Immunodeficiency Virus-Infected Adults Admitted With Sepsis to a Regional Referral Hospital in Uganda. Open Forum Infect Dis. 2019 Mar 14;6(4):ofz140. doi: 10.1093/ofid/ofz140. eCollection 2019 Apr.
PubMed 31024977Mpagama SG, Ndusilo N, Stroup S, Kumburu H, Peloquin CA, Gratz J, Houpt ER, Kibiki GS, Heysell SK. Plasma drug activity in patients on treatment for multidrug-resistant tuberculosis. Antimicrob Agents Chemother. 2014;58(2):782-8. doi: 10.1128/AAC.01549-13. Epub 2013 Nov 18.
PubMed 24247125Heysell SK, Mtabho C, Mpagama S, Mwaigwisya S, Pholwat S, Ndusilo N, Gratz J, Aarnoutse RE, Kibiki GS, Houpt ER. Plasma drug activity assay for treatment optimization in tuberculosis patients. Antimicrob Agents Chemother. 2011 Dec;55(12):5819-25. doi: 10.1128/AAC.05561-11. Epub 2011 Oct 3.
PubMed 21968363Byashalira K, Mbelele P, Semvua H, Chilongola J, Semvua S, Liyoyo A, Mmbaga B, Mfinanga S, Moore C, Heysell S, Mpagama S. Clinical outcomes of new algorithm for diagnosis and treatment of Tuberculosis sepsis in HIV patients. Int J Mycobacteriol. 2019 Oct-Dec;8(4):313-319. doi: 10.4103/ijmy.ijmy_135_19.
PubMed 31793499Otoupalova E, Ampaire L, Null M, Mujaga B, Liu J, Said B, Nuwagira E, Sariko M, Gidoi G, Gulinja A, Jjunju S, Rimoy A, Mwita FC, Kidola J, Atwiine O, Ocaaki D, Munyambalu DK, Rao P, Boulware DR, Thomas TA, Mpagama S, Muzoora C, Heysell SK, Moore CC. Aetiology of sepsis in adults living with HIV in East Africa: a secondary analysis of an open-label, multicentre, randomised, controlled phase 3 trial. EClinicalMedicine. 2026 Jan 28;92:103719. doi: 10.1016/j.eclinm.2025.103719. eCollection 2026 Feb.
PubMed 41768988Heysell SK, Mpagama SG, Nuwagira E, Said B, Conaway M, Null M, Thomas TA, Boulware DR, Otoupalova E, Arinaitwe R, Mushagara R, Edwards L, Buzaare P, Ngoma AM, Muganzi D, Gidoi G, Jjunju S, Gulinja A, Rimoy AG, Mwita FC, Kidola J, Atwiine O, Ocaaki D, Munyambalu DK, Liu J, Ampaire L, Mujaga B, Rao P, Liyoyo A, Sariko M, Muzoora C, Moore CC. Immediate or high-dose antituberculosis therapy for HIV-related sepsis in Tanzania and Uganda (ATLAS): a phase 3, open-label, randomised, controlled, 2 x 2 factorial, superiority trial. Lancet Infect Dis. 2026 Jun;26(6):601-613. doi: 10.1016/S1473-3099(25)00747-9. Epub 2026 Jan 28.
PubMed 41619753Said B, Nuwagira E, Liyoyo A, Arinaitwe R, Gitige C, Mushagara R, Buzaare P, Chongolo A, Jjunju S, Twesigye P, Boulware DR, Conaway M, Null M, Thomas TA, Heysell SK, Moore CC, Muzoora C, Mpagama SG. Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial. BMJ Open. 2022 Jun 6;12(6):e061953. doi: 10.1136/bmjopen-2022-061953.
PubMed 35667721
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Clinical Trial of Early Empiric Anti-Mycobacterium Tuberculosis Therapy for Sepsis in Sub-Saharan Africa
- ClinicalTrials.gov ID
- NCT04618198
- Acronym / sponsor ID
- ATLAS / 22611
- Conditions
- Tuberculosis, HIV I Infection, Sepsis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 437 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 5 Jan 2022 (actual)
- Primary completion
- 27 Dec 2024 (actual)
- Study completion
- 20 May 2025 (actual)
- First posted
- 5 Nov 2020 (actual)
- Results
- Posted 9 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In sub-Saharan Africa, tuberculosis (TB) is the etiology of 25-50% of bloodstream infections (BSIs) and the leading cause of sepsis among people living with HIV. TB BSI is associated with 20-50% mortality, and 20-25% of deaths occur within five days of admission. TB BSI is difficult to identify clinically and microbiologically. Given that the high prevalence of TB BSI is under-recognized, most patients with sepsis in sub-Saharan Africa do not receive early anti-TB therapy. The hypothesis of this study is that immediate and optimally dosed anti-TB therapy will improve 28 day mortality in patients with sepsis in Uganda and Tanzania. Therefore, the overall goal is to conduct a phase 3 multi-site open label 2x2 factorial clinical trial of 1) empiric immediate initiation of anti-TB therapy plus standard care compared to diagnosis dependent anti-TB therapy plus standard care and 2) sepsis-specific dose anti-TB therapy plus standard care compared to conventional WHO weight-based dose anti-TB therapy plus standard care for the treatment of sepsis in people living with HIV admitted to our longstanding collaborative research sites at either the Mbarara Regional Referral Hospital in Mbarara, Uganda, or Kilimanjaro region hospitals in Moshi, Tanzania.
Detailed description
The primary objective of this clinical trial is to:
- To conduct a randomized 2x2 factorial clinical trial of 1) empiric immediate initiation of anti-TB therapy plus standard care vs diagnosis dependent anti-TB therapy plus standard care, 2) sepsis-specific anti-TB therapy plus standard care vs conventional WHO weight-based anti-TB therapy plus standard care for patients presenting with sepsis in Uganda and Tanzania.
1a) To determine if empiric immediate initiation of anti-TB therapy plus standard care improves 28 day mortality compared to diagnosis dependent anti-TB therapy plus standard care.
1b) To determine if sepsis-specific dose anti-TB therapy plus standard care improves 28 day mortality compared to conventional WHO weight-based anti-TB therapy plus standard care.
The secondary objectives include:
- To determine if empiric immediate initiation of anti-TB therapy plus standard care improves in-hospital mortality compared to diagnosis dependent anti-TB therapy plus standard care.
- To determine if sepsis-specific dose anti-TB therapy plus standard care improves in-hospital mortality compared to conventional WHO weight-based anti-TB therapy plus standard care.
- To determine if empiric immediate initiation of anti-TB therapy plus standard care improves 6 month mortality compared to diagnosis dependent anti-TB therapy plus standard care.
- To determine if sepsis-specific dose anti-TB therapy plus standard care improves 6 month mortality compared to conventional WHO weight-based anti-TB therapy plus standard care.
- To determine the safety of increased dose sepsis-specific anti-TB therapy for patients with sepsis
- To determine if early achievement of target serum drug concentrations of isoniazid and rifampin, measured at day-2 of TB treatment, associates with more rapid clinical improvement among patients with confirmed TB.
Participants will be men or women aged ≥18 years living with HIV in Tanzania or Uganda who are admitted to one of the study hospitals with sepsis, defined by a clinical concern for infection, a modified quick sepsis-related organ failure assessment (qSOFA) score ≥2 (Glasgow Coma Scale score <15, a respiratory rate ≥22, or a systolic blood pressure ≤90 mmHg or a mean arterial pressure of ≤65 mmHg). This is a multi-site trial at Kilimanjaro region hospitals in Tanzania (Kibong'oto Infectious Diseases Hospital and Kilimanjaro Christian Medical Centre) and Mbarara Regional Referral Hospital in Mbarara, Uganda. At both regional study sites, clinical trial infrastructure has been developed over multiple TB and non-TB related interventional studies supported by the NIH and other funders including EDCTP, WHO, MRC, and BMGF with associated regulatory standards. Furthermore, both regional hospital systems have large recruitment populations serving mid-sized cities where patients receive local care and as referral hospitals for those from more peripheral settings. The study population will be enrolled from the Emergency or inpatient wards. Admission numbers of eligible patients presenting with sepsis at each site allow for a conservative estimates of 100 patients per country per year to be well within attainment.
After enrollment, patients will be randomized to 1) empiric immediate initiation of anti-TB therapy plus standard care vs diagnosis dependent anti-TB therapy plus standard care and 2) conventional WHO recommended weight-based dose anti-TB therapy with rifampin, isoniazid, pyrazinamide, and ethambutol plus pyridoxine, plus standard therapy; or sepsis-specific dose anti-TB therapy with rifampin (~30mg/kg), isoniazid (~7.5mg/kg), pyrazinamide, and ethambutol plus pyridoxine, plus standard care.
Each individual participant will complete all participant follow-up at 6 months from enrollment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
- Model description
- This is a phase 3, multi-site, open-label, randomized controlled clinical 2x2 factorial superiority trial of a) immediate initiation of anti-TB therapy and b) sepsis-specific dose anti-TB therapy for people living with HIV and presenting with sepsis to our regional study sites in Tanzania and Uganda.
| Arm | Type | Receives |
|---|---|---|
| Diagnosis dependent / conventional dose anti-TB therapy | No intervention | –Standard care per admitting team including ceftriaxone x 7 days If subsequent TB test positive, then WHO recommended weight-based anti-TB therapy x 28 days |
| Immediate anti-TB therapy/conventional dose anti-TB therapy | Experimental | Other: Immediate anti-TB therapyStandard care per admitting team including ceftriaxone x 7 days plus immediate empiric WHO recommended weight-based dose anti-TB therapy x 28 days |
| Diagnosis dependent/sepsis specific dose anti-TB therapy | Experimental | Other: Sepsis-specific dose anti-TB therapyStandard care per admitting team including ceftriaxone x 7 days If subsequent TB test positive, then sepsis specific dose anti-TB therapy x 28 days |
| Immediate anti-TB therapy/sepsis specific dose anti-TB therapy | Experimental | Other: Immediate anti-TB therapy, Other: Sepsis-specific dose anti-TB therapyStandard care per admitting team including ceftriaxone x 7 days plus immediate empiric sepsis specific dose anti-TB therapy x 28 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female aged ≥18 years living with HIV
- Admitted to hospital with 1) clinical concern for infection; 2) ≥2 qSOFA score criteria (Glasgow Coma Scale score <15, a respiratory rate ≥22, or a systolic blood pressure ≤90 mmHg or a mean arterial pressure of ≤65 mmHg)
- Resident within a pre-defined geographic area to ensure TB clinic follow-up
Key exclusion criteria (8 listed)
- Known active TB or receiving anti-TB therapy
- Pregnancy or lactation. Women will undergo urine pregnancy screening. Pregnant women will be excluded due to the possible toxicity and teratogenicity of high dose rifampin and isoniazid included in anti-TB therapy as well as possible teratogenicity of dolutegravir which is recommended as first-line antiretroviral therapy in this study.
- Known allergic reactions to the components of the anti-TB therapy
- Treatment with another investigational drug or other intervention within one month
- Known liver disease
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 |
|---|---|---|
| Immediate anti-TB therapyStudy participants will receive immediate empiric anti-TB therapy | Other | Immediate anti-TB therapy/conventional dose anti-TB therapy, Immediate anti-TB therapy/sepsis specific dose anti-TB therapy |
| Sepsis-specific dose anti-TB therapyStudy participants will receive conventional WHO weight-based dose anti-TB therapy | Other | Diagnosis dependent/sepsis specific dose anti-TB therapy, Immediate anti-TB therapy/sepsis specific dose anti-TB therapy |
Primary outcome
28-day Mortality
Time frame: 28 days from enrollment
number of participants with mortality
13 secondary outcomes
In-hospital Mortality
Time frame: 28 days from enrollment
6-month Mortality
Time frame: 6 months from enrollment
Time to Death
Time frame: 6 months from enrollment
Duration of Hospitalization
Time frame: 6 months from enrollment
Time to Anti-TB Therapy
Time frame: 28 days from enrollment
Adverse Events
Time frame: 28 days from enrollment
Sepsis Etiology
Time frame: baseline specimen collection
Time to Ambulation
Time frame: 28 days from enrollment
Time to Temperature Normalization
Time frame: 28 days from enrollment
Peak Drug Concentration Isoniazid
Time frame: 2 days from enrollment
Peak Drug Concentration Rifampin
Time frame: 2 days from enrollment
Total Drug Exposure Isoniazid
Time frame: 2 days from enrollment
Total Drug Exposure Rifampin
Time frame: 2 days from enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29868873Moore CC, Jacob ST, Banura P, Zhang J, Stroup S, Boulware DR, Scheld WM, Houpt ER, Liu J. Etiology of Sepsis in Uganda Using a Quantitative Polymerase Chain Reaction-based TaqMan Array Card. Clin Infect Dis. 2019 Jan 7;68(2):266-272. doi: 10.1093/cid/ciy472.
- Background: PubMed 31024977Hazard RH, Kagina P, Kitayimbwa R, Male K, McShane M, Mubiru D, Welikhe E, Moore CC, Abdallah A. Effect of Empiric Anti-Mycobacterium tuberculosis Therapy on Survival Among Human Immunodeficiency Virus-Infected Adults Admitted With Sepsis to a Regional Referral Hospital in Uganda. Open Forum Infect Dis. 2019 Mar 14;6(4):ofz140. doi: 10.1093/ofid/ofz140. eCollection 2019 Apr.
- Background: PubMed 24247125Mpagama SG, Ndusilo N, Stroup S, Kumburu H, Peloquin CA, Gratz J, Houpt ER, Kibiki GS, Heysell SK. Plasma drug activity in patients on treatment for multidrug-resistant tuberculosis. Antimicrob Agents Chemother. 2014;58(2):782-8. doi: 10.1128/AAC.01549-13. Epub 2013 Nov 18.
- Background: PubMed 21968363Heysell SK, Mtabho C, Mpagama S, Mwaigwisya S, Pholwat S, Ndusilo N, Gratz J, Aarnoutse RE, Kibiki GS, Houpt ER. Plasma drug activity assay for treatment optimization in tuberculosis patients. Antimicrob Agents Chemother. 2011 Dec;55(12):5819-25. doi: 10.1128/AAC.05561-11. Epub 2011 Oct 3.
- Background: PubMed 31793499Byashalira K, Mbelele P, Semvua H, Chilongola J, Semvua S, Liyoyo A, Mmbaga B, Mfinanga S, Moore C, Heysell S, Mpagama S. Clinical outcomes of new algorithm for diagnosis and treatment of Tuberculosis sepsis in HIV patients. Int J Mycobacteriol. 2019 Oct-Dec;8(4):313-319. doi: 10.4103/ijmy.ijmy_135_19.
- Derived from this study: PubMed 41768988Otoupalova E, Ampaire L, Null M, Mujaga B, Liu J, Said B, Nuwagira E, Sariko M, Gidoi G, Gulinja A, Jjunju S, Rimoy A, Mwita FC, Kidola J, Atwiine O, Ocaaki D, Munyambalu DK, Rao P, Boulware DR, Thomas TA, Mpagama S, Muzoora C, Heysell SK, Moore CC. Aetiology of sepsis in adults living with HIV in East Africa: a secondary analysis of an open-label, multicentre, randomised, controlled phase 3 trial. EClinicalMedicine. 2026 Jan 28;92:103719. doi: 10.1016/j.eclinm.2025.103719. eCollection 2026 Feb.
- Derived from this study: PubMed 41619753Heysell SK, Mpagama SG, Nuwagira E, Said B, Conaway M, Null M, Thomas TA, Boulware DR, Otoupalova E, Arinaitwe R, Mushagara R, Edwards L, Buzaare P, Ngoma AM, Muganzi D, Gidoi G, Jjunju S, Gulinja A, Rimoy AG, Mwita FC, Kidola J, Atwiine O, Ocaaki D, Munyambalu DK, Liu J, Ampaire L, Mujaga B, Rao P, Liyoyo A, Sariko M, Muzoora C, Moore CC. Immediate or high-dose antituberculosis therapy for HIV-related sepsis in Tanzania and Uganda (ATLAS): a phase 3, open-label, randomised, controlled, 2 x 2 factorial, superiority trial. Lancet Infect Dis. 2026 Jun;26(6):601-613. doi: 10.1016/S1473-3099(25)00747-9. Epub 2026 Jan 28.
- Derived from this study: PubMed 35667721Said B, Nuwagira E, Liyoyo A, Arinaitwe R, Gitige C, Mushagara R, Buzaare P, Chongolo A, Jjunju S, Twesigye P, Boulware DR, Conaway M, Null M, Thomas TA, Heysell SK, Moore CC, Muzoora C, Mpagama SG. Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial. BMJ Open. 2022 Jun 6;12(6):e061953. doi: 10.1136/bmjopen-2022-061953.
- Individual participant dataSharing planned: Yes
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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.
Christopher Moore, MD principal investigator
University of Virginia
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Immediate anti-TB therapy and Sepsis-specific dose anti-TB therapy in people with Tuberculosis and HIV I Infection, run by University of Virginia at 2 sites in 2 countries.
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 6 inclusion and 8 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 Sep 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 Tanzania, Uganda. 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?
Yes. Results are posted in the registry (first posted 9 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
28-day Mortality (time frame: 28 days from enrollment). 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 NCT04618198, which also lists 8 linked publications.
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 Sep 2026.