TREATment of Lower Respiratory Tract Infection in Sri Lanka (TREAT-SL) (TREAT-SL)

TREATment of Lower Respiratory Tract Infection in Sri Lanka (TREAT-SL): A Stepped-wedge Cluster Randomized Trial of an Electronic Clinical Decision Support Tool (eCDST) for the Diagnosis and Treatment of Lower Respiratory Tract Infection (LRTI) in Southern Sri Lanka

This is a stepped-wedge, cluster-randomized, two-arm, open-label, clinical trial of an electronic clinical decision support tool (eCDST) for the diagnosis and treatment of lower respiratory tract infection (LRTI) among patients at three sites in Southern Province, Sri Lanka.

The primary objective of this trial is to determine the impact of an electronic clinical decision support tool (eCDST) on clinical outcomes and antibacterial prescription in subjects with LRTI in the intervention group compared to the control group.

The study will enroll 765 patients ≥ 14 years of age. Medical wards will be randomized in clusters to the intervention at intervals of 3-6 months until all clusters cross over. Participants will be followed for 30 days from enrollment to record clinical outcomes and any antimicrobials prescribed.

Study Overview

• Status: Not yet recruiting
• Conditions: Lower Resp Tract Infection
• Intervention / Treatment: Other: electronic clinical decision support tool (eCDST) diagnostic plan

• Study Type: Interventional
• Enrollment (Estimated): 765
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gayani Tillekeratne, MD, MSc; Phone Number: (919) 681-7516; Email: gayani.tillekeratne@duke.edu
• Study Contact Backup: Name: Stefany Olague, MPH; Phone Number: (919)668-8131; Email: stefany.olague@duke.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Admitted within prior 48 hours

2. Have evidence of new acute respiratory illness (<14 days of symptoms), as indicated by at least one of the following:

   1. New cough or sputum production
   2. Chest pain
   3. Dyspnea or tachypnea (respiratory rate >20 breaths/minute)
   4. Abnormal lung examination

3. Have evidence of acute infection, as indicated by at least one of the following:

   1. Self-reported fever or chills
   2. Documented fever ≥38 ̊ C (100.4 ̊ F)
   3. Documented hypothermia <35.5 ̊ C (95.9 ̊ F)
   4. Leukocytosis (white blood cell count >10,000/mm3)
   5. Leukopenia (white blood cell count <3000/mm3)
   6. New altered mental status
4. Ability and willingness of patient, parent or legally authorized representative (LAR) to give informed consent
5. Ability of children 14-17 years of age to provide assent
6. Ability to complete follow-up encounter at 30 days in person or by telephone

Exclusion Criteria:

1. Hospitalized recently (within last 28 days)
2. If they have been enrolled into this clinical trial previously
3. Surgery in the past 7 days
4. If they are unable or unwilling to complete the follow-up encounter
5. If they will likely be transferred from the medical wards within 24 hours of enrollment (to another ward or to another hospital)

6. If they have underlying conditions or circumstances for which physicians would be unlikely to withhold antibacterials:

   1. Vasopressor therapy
   2. Cystic fibrosis
   3. Known severe immunosuppression (i. Cancer or another condition with neutropenia (absolute neutrophil count <1000/ microL; ii. Solid- organ or hematopoietic stem-cell transplant within the previous 90 days; iii. Active graft-versus-host disease or bronchiolitis obliterans; iv. On chronic steroids equivalent to prednisone 20mg daily for ≥ 2 weeks or other targeted cytotoxic or biologic immunosuppressants within the prior 4 weeks; v. Human immunodeficiency virus infection with a CD4 cell count <200/mm3)
   4. Have an accompanying non-respiratory infection
   5. Have evidence of a lung abscess or empyema
   6. Have respiratory failure at enrollment, evidenced by use of non-invasive or invasive ventilation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Arm; Clinicians will be asked to use the diagnostic portion of the electronic clinical decision tool (eCDST) on their mobile phones, into which they will enter inputs and receive a diagnostic plan. Point of care (POC) testing as advised by the eCDST will be conducted by either clinical staff or trained research staff. If performed by research staff, results will be delivered on paper within 6 hours of testing to ≥ 2 primary clinicians on the team (including the consultant/ attending-level physician or senior registrar). THK, DGM, and DGH do not have an electronic medical record system. Clinicians will be asked to input the results from diagnostic testing and to follow the treatment recommendations as per the eCDST, but will be advised that the final decision regarding prescription of antimicrobials is entirely at their discretion.	Other: electronic clinical decision support tool (eCDST) diagnostic plan; Participants will be followed for 30 days from enrollment to record clinical outcomes and any antimicrobials used. Analyses will compare clinical outcomes and antimicrobial use between the intervention arm and usual care.
No Intervention: Usual Care Arm; Study staff will inform the treating clinicians to diagnose and treat patients according to usual practice. Clinicians will be able to order routine diagnostic testing as per standard practice. These tests may include complete blood count, chemistries, C-reactive protein (CRP) testing, erythrocyte sedimentation rate (ESR) testing, blood and sputum cultures, and chest x-ray or chest CT imaging.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total duration of antibacterial prescription for the index visit	Total duration of antibacterial prescription for the index visit will include the number of days that antibacterials are prescribed during the index hospitalization, as well as the number of days that antibacterials are prescribed at discharge from the hospital (intended use).	Index hospitalization, up to approximately 30 days
Composite of adverse outcomes that could be attributed to withholding antibacterials	A binary clinical endpoint consisting of a composite of adverse outcomes that could be attributed to withholding antibacterials. These outcomes would not be present at enrollment, and could occur anytime until Day 30.	Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants using non-invasive ventilation	Use of non-invasive ventilation (i.e., continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP]) for treatment of the acute illness )	Day 30
Proportion of participants using mechanical ventilation	Use of mechanical ventilation (via endotracheal tube)	Day 30
Proportion of participants readmitted to the hospital	Proportion of participants readmitted to the hospital	Day 30
Proportion of deaths	Proportion of deaths	Day 30
Proportion of participants seeking subsequent outpatient care for the LRTI illness and receiving an antibacterial prescription	Proportion of participants seeking subsequent outpatient care for the LRTI illness and receiving an antibacterial prescription	Day 30
Proportion of participants admitted to the intensive care unit (ICU) during index hospitalization	Proportion of participants admitted to the intensive care unit (ICU) during index hospitalization	Index hospitalization, up to approximately 30 days
Duration of admission to the intensive care unit (ICU) during index hospitalization	Duration of admission to the intensive care unit (ICU) during index hospitalization	Index hospitalization, up to approximately 30 days
Number of participants requiring use of supplemental oxygen by nasal cannula or face mask during index hospitalization	Number of participants requiring use of supplemental oxygen by nasal cannula or face mask during index hospitalization	Index hospitalization, up to approximately 30 days
Duration of supplemental oxygen by nasal cannula or face mask during index hospitalization	Duration of supplemental oxygen by nasal cannula or face mask during index hospitalization	Index hospitalization, up to approximately 30 days
Duration of non-invasive ventilation during index hospitalization	Duration of non-invasive ventilation during index hospitalization	Index hospitalization, up to approximately 30 days
Duration of mechanical ventilation during index hospitalization	Duration of mechanical ventilation during index hospitalization	Index hospitalization, up to approximately 30 days
Duration of index hospitalization	Duration of index hospitalization	Index hospitalization, up to approximately 30 days
Proportion prescribed antibacterials- cumulative	Any prescription of antibacterials from enrollment to the point of assessment will be considered prescription of antibacterials.	Day 1, Day 2, Day 3, by discharge, and by Day 30
Proportion prescribed antibacterials- at time of assessment	Prescription of antibacterials will only be assessed at the specific time of assessment	Day 1, Day 2, Day 3, by discharge, and by Day 30
Total antibacterial exposure per patient during hospitalization	This is defined as the total number of days prescribed an antibacterial	Day 30
Proportion prescribed oseltamivir- cumulative	Any prescription of oseltamivir from enrollment to the point of assessment will be considered prescription of oseltamivir	Day 1, Day 2, Day 3, at discharge, and by Day 30
Proportion prescribed oseltamivir- at time of assessment	Prescription of oseltamivir will only be assessed at the specific time of assessment	Day 1, Day 2, Day 3, at discharge, and by Day 30
Total oseltamivir exposure per patient during hospitalization	This is defined as the total number of days prescribed oseltamivir	Day 30
Proportion prescribed SARS-CoV-2 antivirals during hospitalization- cumulative	Any prescription of SARS-CoV-2 antivirals from enrollment to the point of assessment will be considered prescription of SARS-CoV-2 antivirals	Day 1, Day 2, Day 3, at discharge, and by Day 30
Proportion prescribed SARS-CoV-2 antivirals during hospitalization- at time of assessment	Prescription of SARS-CoV-2 antivirals will only be assessed at the specific time of assessment	Day 1, Day 2, Day 3, at discharge, and by Day 30
Physician adherence, as measured by proportion in whom the first recommended diagnostic test (if recommended) was performed	Physician adherence to the eCDST diagnostic recommendations within 24 hours of receiving recommendations, in the intervention group.	24 hours
Physician adherence, as measured by the proportion in whom the second recommended diagnostic test (if recommended) was performed	Physician adherence to the eCDST diagnostic recommendations within 48 hours of receiving recommendations, in the intervention group.	48 hours
Physician adherence, as measured by proportion in whom the antibacterial treatment recommendation was followed	Physician adherence, as measured by proportion in whom the antibacterial treatment recommendation was followed	24 hours and 48 hours
Physician adherence, as measured by the proportion in whom the oseltamivir treatment recommendation was followed	Physician adherence, as measured by the proportion in whom the oseltamivir treatment recommendation was followed	24 hours and 48 hours
Physician adherence, as measured by the proportion in whom all treatment recommendations were followed	Physician adherence, as measured by the proportion in whom all treatment recommendations were followed	24 hours and 48 hours

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Gayani Tillekeratne, MD, MSc, Duke University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: March 25, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: eCDST
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Infections; Communicable Diseases; Respiratory Tract Infections
• Other Study ID Numbers: Pro00114347; R01AI168420 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No