Early Empiric Anti-Mycobacterium Tuberculosis Therapy for Sepsis in Sub-Saharan Africa
NCT ID: NCT04618198
Last Updated: 2023-03-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
UNKNOWN
PHASE3
436 participants
INTERVENTIONAL
2021-12-10
2025-06-25
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
TMC207-TiDP13-C208: Anti-bacterial Activity, Safety, and Tolerability of TMC207 in Participants With Multi-drug Resistant Mycobacterium Tuberculosis (MDR-TB).
NCT00449644
STeroids and Enhanced Spectrum Antibiotics for the Treatment of Patients in Africa With Refractory Sepsis
NCT07332325
To Evaluate the Safety, Tolerability, and Efficacy of TMC207 as Part of an Individualized Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Participants With Sputum Smear-positive Pulmonary MDR-TB.
NCT00910871
Prospective Study of Methicillin-Resistant Staphylococcus Aureus (MRSA) Among HIV-Infected Persons
NCT00631566
A Study to Evaluate the Safety and Efficacy of Azithromycin in Individual Patients With Serious Nontuberculous Mycobacterial Disease Who Are Failing or Intolerant of Other Available Therapy
NCT00002085
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
1\) 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:
1. 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.
2. 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.
3. 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.
4. 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.
5. To determine the safety of increased dose sepsis-specific anti-TB therapy for patients with sepsis
6. 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
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
FACTORIAL
TREATMENT
SINGLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Diagnosis dependent / conventional dose anti-TB therapy
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
No interventions assigned to this group
Immediate anti-TB therapy/conventional dose anti-TB therapy
Standard care per admitting team including ceftriaxone x 7 days plus immediate empiric WHO recommended weight-based dose anti-TB therapy x 28 days
Immediate anti-TB therapy
Study participants will receive immediate empiric anti-TB therapy
Diagnosis dependent/sepsis specific dose anti-TB therapy
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
Sepsis-specific dose anti-TB therapy
Study participants will receive conventional WHO weight-based dose anti-TB therapy
Immediate anti-TB therapy/sepsis specific dose anti-TB therapy
Standard care per admitting team including ceftriaxone x 7 days plus immediate empiric sepsis specific dose anti-TB therapy x 28 days
Immediate anti-TB therapy
Study participants will receive immediate empiric anti-TB therapy
Sepsis-specific dose anti-TB therapy
Study participants will receive conventional WHO weight-based dose anti-TB therapy
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Immediate anti-TB therapy
Study participants will receive immediate empiric anti-TB therapy
Sepsis-specific dose anti-TB therapy
Study participants will receive conventional WHO weight-based dose anti-TB therapy
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female aged ≥18 years living with HIV
4. 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)
5. Resident within a pre-defined geographic area to ensure TB clinic follow-up
6. For females of reproductive potential: use of highly effective contraception through 28 days
Exclusion Criteria
2. 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.
3. Known allergic reactions to the components of the anti-TB therapy
4. Treatment with another investigational drug or other intervention within one month
5. Known liver disease
6. 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
7. Positive serum cryptococcal antigen test
8. Current treatment with a drug known to have significant interaction with anti-TB therapy
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
University of Virginia
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Scott Heysell, MD
Associate Professor, Infectious Disease
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Christopher Moore, MD
Role: PRINCIPAL_INVESTIGATOR
University of Virginia
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Kibong'oto Infectious Diseases Hospital
Sanya Juu, , Tanzania
Mbarara University Science Technology
Mbarara, , Uganda
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
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.
Hazard 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.
Mpagama 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.
Heysell 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.
Byashalira 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.
Said 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.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
22611
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.