Trial design:

Randomised controlled, two-arm, parallel, clinical trial to assess the efficacy and safety of sequential daily procalcitonin assessments to guide de-escalation of empirical antibiotic therapy in adult patients with sepsis.

Trial settings Trial site is Chattogram Medical College Hospital (CMCH), Bangladesh. CMCH is tertiary care hospital with undergraduate and postgraduate teaching facilities. This tertiary hospital receives referrals from urban and rural areas of southern Bangladesh and has basic facilities for intensive care and haemodialysis.

Trial Participants:

Male or female hospitalised patients, 16-65 years of age, with confirmed or suspected sepsis Patients (Total 532) will be 1:1 randomised to either:

• Intervention arm: daily measurement of serum procalcitonin concentrations to guide de-escalation of antibiotics (Intervention arm: 266), or
• Control arm: standard of practice to guide de-escalation of antibiotics without procalcitonin assessments (Control arm: 266).

Patients will be followed-up until ICU discharge and/or hospital discharge with an additional follow-up at 28 days after discharge.

Funder: Wellcome Trust of Great Britain

Grant reference number from Wellcome Trust: 220211/A/20/Z

Inclusion Criteria:

• Participant, legally authorised person/ legal guardian willing and able to give informed consent for participation in the trial.
• Male or Female, aged 16 to 65 years
• Suspected or proven bacterial infection
• A positive sepsis screening National Early Warning Score (NEWS) equal or greater than 5 (Table 1 or at least one criterion with a score of 3.
• Intention to start parenteral antibiotic therapy
• Within 24 hours of hospital admission

Exclusion Criteria:

• Patients with suspected/documented tuberculosis, parasitic infection (including malaria or visceral leishmaniasis), or viral infections (i.e., COVID-19, dengue, HIV)
• Pregnancy
• Intended for a short stay in ICU or general ward (such as post-operative)
• Patients requiring a predefined long course of antibiotic therapy (such as endocarditis, osteomyelitis, lung abscess, liver abscess, septic arthritis)
• Immunocompromised patients, including as severe neutropenia (< 500 cells/ml), transplant recipients, on prolonged corticosteroid treatment, chemotherapy or disease modifying immunomodulatory medications
• More than 48 hours of parenteral antibiotic use
• Surgical patients, including patients with a surgical septic source or patients requiring source control, i.e. abscess drainage
• Moribund patients or patients receiving end of life care
• Previous enrolment in PROCALBAN
• Conditions accompanied with a systemic inflammatory state, including pancreatitis, cardiogenic shock, severe trauma

Participant data and results from blood analyses stored in the database may be shared according to the terms defined in the Mahidol Oxford Tropical Medicine Research Unit (MORU) data sharing policy with other researchers to use in the future. Datasets will be de-identified to ensure patient privacy and confidentiality.

Procalcitonin measurements.