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SepsisPhase 3STARSNCT07332325

STeroids and Enhanced Spectrum Antibiotics for the Treatment of Patients in Africa With Refractory Sepsis

A Phase 3 study testing Hydrocortisone administration and Expanded antimicrobial therapy in people with Sepsis and Tuberculosis, run by University of Virginia at 4 sites in 2 countries.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

Sepsis, a life-threatening condition due to a dysregulated response to infection, is the leading cause of global mortality and is frequently driven by tuberculosis (TB) and drug-resistant bacteria in sub-Saharan Africa, particularly among people living with HIV. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sepsis, Tuberculosis
What is being tested?
Hydrocortisone administration and Expanded antimicrobial therapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
344 participants
Where
4 sitesin 2 countries
Study dates
Oct 2026to Sep 2029
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

  • 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 people will be excluded due to lack of pharmacokinetic data for the expanded antibiotic regimen in pregnancy.
  • Known allergic reactions to the components of the interventional 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
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  • Positive serum cryptococcal antigen test
  • Current treatment with a drug known to have significant, non-correctable interaction with anti-TB therapy
  • Already receiving corticosteroids at the time of presentation to the hospital

Trial locations and contacts

4 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Scott K Heysell, MD, MPH contact

434-924-0000 ext. 6962

SKH8R@uvahealth.org

Christopher C Moore, MD contact

434-924-0000 ext. 3489

ccm5u@uvahealth.org

4 sites in 2 countries

Tanzania2 sites
  • Sekou Toure Regional Referral Hospital

    Mwanza

    Frederick C Mwita, MD, +255282502171, Cyprianfredy@gmail.com

    Frederick C Mwita, MD

  • Kibong'oto Infectious Diseases Hospital

    Sanya Juu

    Stellah G Kibong'oto, MD, PhD, +255272974140, sempagama@yahoo.com

    Bibie Said, MD, +255272974140, bibiesd90@gmail.com

Other trials in Tanzania

Uganda2 sites
  • Fort Portal Regional Referral Hospital

    Fort Portal

    Dalton K Munyambalu, MBChB, MMed, +256 717 555139, daltonkamuda@gmail.com

    Dalton K Munyambalu, MBChB, MMed

  • Mbarara Regional Referral Hospital

    Mbarara

    Edwin Nuwagira, MBChB, MMed, +256485420030, enuwagira@must.ac.ug

    Edwin Nuwagira, MBChB, MMed

Other trials in Uganda

About this study

Official title: STeroids and Enhanced Spectrum Antibiotics for the Treatment of Patients in Africa With Refractory Sepsis (STARS Trial)

Sepsis, a life-threatening condition due to a dysregulated response to infection, is the leading cause of global mortality and is frequently driven by tuberculosis (TB) and drug-resistant bacteria in sub-Saharan Africa, particularly among people living with HIV. The prevailing standard of care in the region, ceftriaxone alone, is insufficient as it does not address TB, drug-resistant bacteria, or adrenal insufficiency, which is common in HIV-related sepsis. Therefore, the investigators propose a randomized 2x2 factorial clinical trial to compare 28-day survival from sepsis between study participants who along with a standard of care that includes immediate conventional anti-TB treatment receive 1) hydrocortisone to treat septic shock and 2) rifampin, isoniazid, levofloxacin and linezolid to treat TB and other drug-resistant bacteria in order to deliver important and scalable knowledge that may alter the standard of care for sepsis in HIV endemic settings of sub-Saharan Africa. Improving understanding of the physiology and treatment alternatives for HIV related critical illness globally will have reciprocal benefit for health in the U.S.

Read the detailed description

Sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to infection and is the leading cause of global mortality. The World Health Organization has declared sepsis a global priority. Yet, little is known about sepsis in the global South and specifically sub-Saharan Africa where there are an estimated 17 million cases and 3.5 million attributable deaths per year. The majority of these patients are living with human immunodeficiency virus (HIV). The investigators have determined the leading cause of sepsis in this region is tuberculosis (TB) which is responsible for 25-30% of bloodstream infections in septic patients. TB sepsis is associated with 20-50% mortality rates with the majority of deaths occurring within the first 4-5 days of admission. Other causative pathogens include bacteria commonly or intrinsically resistant to third-generation cephalosporins which are the standard antimicrobial treatment for sepsis adopted from the global North. The investigators have also studied anti-TB pharmacokinetics/pharmacodynamics in septic patients and discovered considerably low circulating drug concentrations that are suboptimal for microbial kill. Concurrently, the investigators have also found a high burden of corticosteroid insufficiency in people with critical illness at collaborative study sites in Uganda and Tanzania. HIV and TB, independently and in combination, contribute to adrenal infection and endogenous steroid insufficiency. In further observational study, adults with sepsis at the collaborative study sites treated with corticosteroids have significantly improved survival from septic shock in-line with some, but not all, trials of adjunctive steroids in infection associated critical illness. Therefore, hypotheses are that immediate hydrocortisone administered over 7 days followed by a 7-day taper will improve 28 day mortality compared to the standard of care where corticosteroids are not administered, and that an enhanced antimicrobial regimen for 14 days to target TB and other drug-resistant bacteria of sepsis (rifampin, isoniazid, levofloxacin and linezolid) will improve 28 day mortality compared to the standard of care of immediate conventional anti-TB treatment and ceftriaxone alone. These hypotheses will be tested through a randomized 2x2 factorial clinical trial where participants hospitalized with HIV and sepsis will be randomized to 1) hydrocortisone or the standard care without hydrocortisone, and 2) the enhanced antimicrobial regimen plus ceftriaxone or the standard care with ceftriaxone alone. This randomized 2x2 factorial clinical trial is strongly endorsed by Tanzanian and Ugandan stakeholders, utilizes drugs that are available within national formularies and regional pharmacies, and if successful will be scalable for adults with sepsis in HIV endemic regions of sub-Saharan Africa. Improved understanding of the physiology and treatment alternatives for HIV related critical illness globally will have reciprocal benefit for health in the U.S.

Conditions
Sepsis, Tuberculosis
Being tested
Hydrocortisone administration, Expanded antimicrobial therapy
Keywords
Sepsis, HIV, tuberculosis, Africa
Medical subject headings
Sepsis, Tuberculosis

What participants receive

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

  • Hydrocortisone administrationDrug

    Immediate hydrocortisone at 200 mg IV daily for 7 days and a tapering schedule for an additional 7 days

  • Expanded antimicrobial therapyDrug

    empiric initiation of the enhanced spectrum antimicrobial therapy regimen (rifampin, isoniazid, linezolid, and levofloxacin) for 14 days plus standard care which includes ceftriaxone for 7 days or diagnosis dependent conventional anti-TB therapy

Study groups in NCT07332325
Study groupRoleWhat they receive
No hydrocortisone/immediate anti-TB therapyNo interventionStandard of care
Hydrocortisone/immediate anti-TB therapyExperimentalNot described
Receives: Drug: Hydrocortisone administration
No hydrocortisone/enhanced spectrum antimicrobial therapyExperimentalNot described
Receives: Drug: Expanded antimicrobial therapy
Hydrocortisone/enhanced spectrum antimicrobial therapyExperimentalNot described
Receives: Drug: Hydrocortisone administration; Drug: Expanded antimicrobial therapy

What is being measured

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

  1. Mortality

    Primary outcome measure

    Measured: 28 days from date of randomization

Secondary outcomes (16)
  1. In-hospital mortality

    Mortality

    Measured: from enrollment through hospitalization, an average of 14 days

  2. 6-month mortality

    Mortality

    Measured: From the date of randomization until death or 180 days from randomization

  3. Time to death

    Mortality

    Measured: From date of randomization to death or 180 days from randomization

  4. Incidence of new post-admission shock

    New post-admission shock

    Measured: From the time of enrollment through hospital discharge, an average of 14 days

  5. Duration of hospitalization

    Duration of hospitalization

    Measured: From the time of randomization until date of hospital discharge up to 180 days, or death if before hospital discharge

  6. Volume of IV fluids received

    Volume of IV fluids received

    Measured: From the date of randomization until date of hospital discharge up to 180 days, or date of death if occurring before discharge

  7. Adverse drug events during the 28-day study period

    Adverse drug events

    Measured: From date of randomization to 28 days post randomization or date of death if death occurred before 28 days

  8. Time to ambulation

    Time to ambulation

    Measured: From date of randomization until the date of first documented ambulation during hospitalization, or date of death from any cause, whichever came first, on average over 14 days, but up to 180 days

  9. Time to temperature normalization

    Time to temperature normalization

    Measured: From date of randomization until the date of first documented normal temperature during hospitalization, or date of death from any cause, whichever came first, on average over 14 days, but up to 180 days

  10. Lactate/delta lactate

    Lactate concentration change

    Measured: From the date of randomization until the date of hospital discharge or the date of death if death occurred before discharge, on average 14 days

  11. Capillary fill time/delta capillary fill time

    Change in capillary fill time

    Measured: From the date of randomization until the date of hospital discharge or the date of death if death occurred before discharge, on average 14 days

  12. Universal Vital Assessment score and delta Universal Vital Assessment score: component number one, heart rate

    Calculation of initial Universal Vital Assessment mortality risk score at randomization and 72 hours after randomization: component number one, measure heart rate

    Measured: From the time of randomization to 72 hours after randomization

  13. Universal Vital Assessment mortality risk score at randomization and 72 hours after randomization: component number two, respiratory rate

    Calculation of initial Universal Vital Assessment mortality risk score at randomization and 72 hours after randomization: component number two, measure respiratory rate

    Measured: From time to randomization to 72 hours

  14. Calculation of initial Universal Vital Assessment mortality risk score at randomization and 72 hours after randomization: component number three, systolic blood pressure

    Calculation of initial Universal Vital Assessment mortality risk score at randomization and 72 hours after randomization: component number three, measure systolic blood pressure

    Measured: From time to randomization to 72 hours

  15. Calculation of initial Universal Vital Assessment mortality risk score at randomization and 72 hours after randomization: component number four, oxygen saturation

    Calculation of initial Universal Vital Assessment mortality risk score at randomization and 72 hours after randomization: component number four, measure oxygen saturation

    Measured: From time to randomization to 72 hours

  16. Calculation of initial Universal Vital Assessment mortality risk score at randomization and 72 hours after randomization: component number five, glascow coma scale

    Calculation of initial Universal Vital Assessment mortality risk score at randomization and 72 hours after randomization: component number five, record record level of consciousness by glascow come scale

    Measured: From time to randomization to 72 hours

Timeline

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

  1. First posted12 Jan 2026
  2. Study startOct 2026 (estimated)
  3. Primary completionMar 2029 (estimated)
  4. Study completionSep 2029 (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
Factorial
Masking
None (open label)
Enrolment
344 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07332325
Sponsor's protocol ID
HSR302304
Other IDs
1U01AI192033-01
Acronym
STARS
Status last verified
May 2026
First submitted
6 Jan 2026
Last updated
1 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Hydrocortisone administration and Expanded antimicrobial therapy in people with Sepsis and Tuberculosis, run by University of Virginia at 4 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 9 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: opening soon, as of the sponsor's last update on 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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?

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?

Contact Scott K Heysell, MD, MPH (434-924-0000 ext. 6962, SKH8R@uvahealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mortality (time frame: 28 days from date of randomization). 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 1 Jun 2026.

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