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

Study Overview
=================
Brief Summary
-----------------
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

Official Title
-----------------
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 Randomised, Controlled, Open-label Trial

Conditions
-----------------
Sepsis

Intervention / Treatment
-----------------
* Procedure: Procalcitonin measurement


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

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 hospitalisation 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 | 
| Overall mortality, mortality associated with recurrent infection and non-lethal recurrent infections. | Recurrent infections include culture positive relapse (failure of initial eradicative treatment for the original infecting strain), culture negative relapse (recurrence of initial symptoms within 2 days of stopping antibiotics) and reinfection (infection with a different strain of the same species). Recurrent infections are defined as growth of one or more of the initial causative bacterial strains (i.e., same genus, species) from a second sample taken from the same infection site after stopping of antibiotic therapy, combined with clinical signs and symptoms of infection. Superinfection is defined as the isolation from the same or another site of one or more pathogens different from that identified during the first infectious episode, together with clinical signs or symptoms of infection. | 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 |