STeroids and Enhanced Spectrum Antibiotics for the Treatment of Patients in Africa With Refractory Sepsis
Trial statusNot yet recruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Virginia
About this 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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
Trial design
Design model
Factorial
Treatments tested in this trial
Hydrocortisone administration
DrugImmediate hydrocortisone at 200 mg IV daily for 7 days and a tapering schedule for an additional 7 days
Expanded antimicrobial therapy
Drugempiric 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
Treatment groups
344 Participants
are divided into 4 treatment groupsGroup A: No hydrocortisone/immediate anti-TB therapyNo intervention 0 interventions
Group B: Hydrocortisone/immediate anti-TB therapyExperimental treatment 1 intervention
Group C: No hydrocortisone/enhanced spectrum antimicrobial therapyExperimental treatment 1 intervention
Group D: Hydrocortisone/enhanced spectrum antimicrobial therapyExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Mortality
Primary outcome measure
Time frame
28 days from date of randomizationSecondary outcomes
1
In-hospital mortality
Mortality
Time frame
from enrollment through hospitalization, an average of 14 days2
6-month mortality
Mortality
Time frame
From the date of randomization until death or 180 days from randomization3
Time to death
Mortality
Time frame
From date of randomization to death or 180 days from randomization4
Incidence of new post-admission shock
New post-admission shock
Time frame
From the time of enrollment through hospital discharge, an average of 14 daysSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Virginia
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator
Source ClinicalTrials.gov
This trial is not recruiting at the moment. You can still explore other options: