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

NCT07332325 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: HSR3023041U01AI192033-01
• Study Type: interventional
• Target: 344
• Locations: 2 countries
• Sites: 4

Brief 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. The current standard of care in the region, ceftriaxone, 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 the standard of care 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.

Conditions

Sepsis; Tuberculosis

Keywords

Sepsis; HIV; tuberculosis; Africa

Outcome Measures

Primary Outcomes (1)

• Mortality

  Primary outcome measure

  28 days from date of randomization

Secondary Outcomes (16)

• In-hospital mortality

  from enrollment through hospitalization, an average of 14 days

• 6-month mortality

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

• Time to death

  From date of randomization to death or 180 days from randomization

• Incidence of new post-admission shock

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

• Duration of hospitalization

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

Study Arms (4)

No hydrocortisone/standard antimicrobial therapy

NO INTERVENTION

Standard of care

Hydrocortisone/standard antimicrobial therapy

EXPERIMENTAL

Drug: Hydrocortisone administration

No hydrocortisone/enhanced spectrum antimicrobial therapy

EXPERIMENTAL

Drug: Expanded antimicrobial therapy

Hydrocortisone/enhanced spectrum antimicrobial therapy

EXPERIMENTAL

Drug: Hydrocortisone administration; Drug: Expanded antimicrobial therapy

Interventions

Hydrocortisone administration DRUG

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

Hydrocortisone/enhanced spectrum antimicrobial therapy; Hydrocortisone/standard antimicrobial therapy

Expanded antimicrobial therapy DRUG

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

Hydrocortisone/enhanced spectrum antimicrobial therapy; No hydrocortisone/enhanced spectrum antimicrobial therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Virginia: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (4)

Sekou Toure Regional Referral Hospital

Mwanza, Tanzania

Location

Kibong'oto Infectious Diseases Hospital

Sanya Juu, Tanzania

Location

Fort Portal Regional Referral Hospital

Fort Portal, Uganda

Location

Mbarara Regional Referral Hospital

Mbarara, Uganda

Location

MeSH Terms

Conditions

Sepsis; Tuberculosis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Study Officials

• Scott K Heysell, MD, MPH

  University of Virginia

  PRINCIPAL INVESTIGATOR

• Christopher C Moore, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Scott K Heysell, MD, MPH

CONTACT

434-924-0000; SKH8R@uvahealth.org

Christopher C Moore, MD

CONTACT

434-924-0000; ccm5u@uvahealth.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 12, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Within one year of trial completion

Locations

UG (2); TA (2)