A Phase 3 interventional study of Hydrocortisone administration and Expanded antimicrobial therapy in Sepsis and Tuberculosis, sponsored by University of Virginia. Not yet recruiting at 4 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-01.
Sponsored by University of Virginia · Phase 3, Interventional, and Treatment
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.
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.
2,416 studies on the registry are indexed under Sepsis; 541 are open to participants now.
This study's planned enrollment of 344 is above the median of 102 across 1,165 interventional studies indexed under Sepsis.
Browse Sepsis studies →University of Virginia is the lead sponsor of 675 studies on the registry; 138 are open to participants now.
Of its 61 completed or terminated interventional studies of FDA-regulated products, 42 (69%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Standard of care
Drug: Hydrocortisone administration
Drug: Expanded antimicrobial therapy
Drug: Hydrocortisone administration · Drug: Expanded antimicrobial therapy
Immediate hydrocortisone at 200 mg IV daily for 7 days and a tapering schedule for an additional 7 days
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
Mortality
Primary outcome measure
Time frame: 28 days from date of randomization
In-hospital mortality
Mortality
Time frame: from enrollment through hospitalization, an average of 14 days
6-month mortality
Mortality
Time frame: From the date of randomization until death or 180 days from randomization
Time to death
Mortality
Time frame: From date of randomization to death or 180 days from randomization
Incidence of new post-admission shock
New post-admission shock
Time frame: From the time of enrollment through hospital discharge, an average of 14 days
Duration of hospitalization
Duration of hospitalization
Time frame: From the time of randomization until date of hospital discharge up to 180 days, or death if before hospital discharge
Volume of IV fluids received
Volume of IV fluids received
Time frame: From the date of randomization until date of hospital discharge up to 180 days, or date of death if occurring before discharge
Adverse drug events during the 28-day study period
Adverse drug events
Time frame: From date of randomization to 28 days post randomization or date of death if death occurred before 28 days
Time to ambulation
Time to ambulation
Time frame: 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
Time to temperature normalization
Time to temperature normalization
Time frame: 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
Lactate/delta lactate
Lactate concentration change
Time frame: 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
Capillary fill time/delta capillary fill time
Change in capillary fill time
Time frame: 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
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
Time frame: From the time of randomization to 72 hours after randomization
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
Time frame: From time to randomization to 72 hours
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
Time frame: From time to randomization to 72 hours
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
Time frame: From time to randomization to 72 hours
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
Time frame: From time to randomization to 72 hours
Plan to share: Yes
Supporting information: Study protocol
Time frame: Within one year of trial completion
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