Use of Procalcitonin, a Blood Test to Guide Antibiotic Therapy for Sepsis in Adults (PROCALBAN)

Use of Procalcitonin Point-of-care Test to Guide De-escalation of Empiric Antibiotic Therapy in Adult Patients With Sepsis in a Tertiary Hospital in Bangladesh (PROCALBAN): a Phase 3 Randomised, Controlled, Open-label Trial

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

Study Overview

• Status: Completed
• Conditions: Sepsis
• Intervention / Treatment: Procedure: Procalcitonin measurement

• Study Type: Interventional
• Enrollment (Actual): 532
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bangladesh
  • Chattogram
    • Chittagong, Chattogram, Bangladesh, 4203
      • Chattogram Medical College Hospital (CMCH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daily measurement of serum procalcitonin concentrations	Procedure: Procalcitonin measurement; Daily measurement of serum procalcitonin concentrations to guide de-escalation of antibiotics
No Intervention: Standard of practice (routine clinical care)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of antibiotic treatment	number of days of antibiotic treatment during the study period.	Through study completion, an average of 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consumption of antibiotics expressed as the Defined Daily Dosage (DDD)	Defined daily dose (DDD) is the assumed average maintenance dose per day for a drug used in its main indication in adults.	Through study completion, an average of 1 month
Days of therapy with antibiotics (DOT)	Definition of DOT: One DOT represents the administration of a single antibiotic on a given day regardless of the number of doses administered or dosage strength. If a patient receives more than one antibiotic it will be added on with DOT of the first antibiotic.	Through study completion, an average of 1 month
Number of days of parenteral antibiotic during hospitalisation period	Number of days of parenteral antibiotic from the day of enrolment to the day of stopping of parenteral antibiotic during hospitalisation period	Through study completion, an average of 1 month
Duration of hospital stay (ICU/ general ward)		Through study completion, an average of 1 month
Proportion of patients with infections caused by antibiotic resistant bacteria		Through study completion, an average of 1 month
Direct medical costs of prescribed antibiotics, the assessment of serum procalcitonin (PCT assay) and hospital stay cost.		Through study completion, an average of 1 month
Number of days of antibiotic treatment during the hospitalisation period.		Through study completion, an average of 1 month
Overall mortality, mortality associated with recurrent infection and non-lethal recurrent infections.	Recurrent infections are classified as follows: culture-positive relapse (unsuccessful eradication of the original infecting strain), culture-negative relapse (reappearance of symptoms after antibiotics cessation with negative cultures), reinfection (infection by a different strain of the same species), and syndromic recurrence (symptoms recur post-antibiotics, regardless of culture results).	Through study completion, an average of 1 month

Collaborators and Investigators

• Sponsor: University of Oxford
• Investigators: Principal Investigator: Arjen Dondorp, Professor, Mahidol Oxford Tropical Medicine Research Unit

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2023
• Primary Completion (Actual): June 20, 2024
• Study Completion (Actual): July 30, 2024

Study Registration Dates

• First Submitted: June 22, 2023
• First Submitted That Met QC Criteria: July 12, 2023
• First Posted (Actual): July 21, 2023

Study Record Updates

• Last Update Posted (Estimated): November 26, 2024
• Last Update Submitted That Met QC Criteria: November 22, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: BAC23002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No