PREDICATE Trial For Respiratory Tract Infections

January 13, 2025 updated by: Prof. Timothy Hudson RAINER, The University of Hong Kong

Early Prednisolone for Suspected Community-acquired Acute Respiratory Tract Infection (PREDICATE): A Double-blind, Randomised, Multi-centre, Adaptive Platform, Controlled Trial

Background

The goal of this clinical trial is to learn if prednisolone works to treat moderate to severe respiratory tract infections in adults admitted to hospital. It will also learn about the safety of prednisolone in this context. The main questions it aims to answer are:

Does prednisolone lower the number of participants who develop sepsis or who survive? What medical problems do participants have when taking prednisolone? Researchers will compare prednisolone to a placebo (a look-alike substance that contains no drug) to see if prednisolone works to treat respiratory tract infections in adults.

Participants will:

Take prednisolone 30mg or a placebo every day for 5 days. Complete a daily diary of symptoms for 30 days and have telephone follow up. Investigators propose to recruit 1300 patients, 650 in each group. The Trial will be conducted in the Emergency Departments and wards of hospitals in Hong Kong.

Investigators expect the proportion of patients admitted to the hospital who develop sepsis or who die within 30 days to be reduced from 25% to 18% after taking active treatment. Secondly, investigators expect any difference in the proportion of patients with Serious adverse events(SAEs) not to exceed 5% between active treatment group and control.

Benefits to Hong Kong and Worldwide: Active treatments (e.g. prednisolone are cheap, HK$0.2 per 5mg tablet) are widely available across the world. Any reduction of progression to sepsis and death if applied worldwide would improve the lives of millions of patients and save millions of dollars of healthcare costs.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Introduction Acute Respiratory Infections (ARIs) are the fourth leading cause of death worldwide, third in China and second in Hong Kong. They are usually caused by bacteria or viruses and are associated with an early hyperinflammatory response. Evidence for the early detection of the disease and pathogen, risk-stratification and management are high priorities for the World Health Organisation (WHO).

The pathogens most likely to cause annual epidemics and pandemics are respiratory viruses although bacteria may cause up to 50% of ARI in hospitalised patients. Despite individual variation, the clinical course of ARIs generally involves an incubation period that lasts hours to days; and an early inflammatory prodrome which lasts days to a week and is characterised by symptoms such as a cough, fever, lethargy, headache (stage I). Whilst most patients recover, some progress to Stage II respiratory deterioration in the subsequent week; and Stage III severe respiratory failure may occur over subsequent weeks. The kinetics of bacterial and viral replication can last up to and even longer than 21 days. This prolonged and relatively slow progression provides several windows of opportunity in which early anti-inflammatory and immunomodulatory therapies could influence the course of the disease, reduce early hyperinflammation, facilitate recovery and well-being, and reduce hospital stay, disease progression, need for intensive care and mortality.

Usual care (UC) for patients with ARI presenting to EDs in Hong Kong is like other primary care settings in the world. For example, in Europe, early treatments are highly variable and consist of paracetamol, non-steroidal anti-inflammatory drugs, low-dose corticosteroids, over-the-counter medicines, fluids, rest, time off school/work, and antibiotics or antivirals. Rapid diagnostic tests (RDTs) are rarely available in the emergency department (ED) and even after admission a pathogen may not be identified in up to 70% of cases. Thus, treatment is usually begun and continued without an identifiable bacterial and/or viral pathogen. As many ARIs follow generic hyperinflammatory pathways, evaluating and repurposing existing anti-inflammatory drugs (e.g. prednisolone, 12) is a common and reasonable strategy which could have relevance not only for Hong Kong but worldwide.

Adaptive Platform Design and Response Adaptive Randomisation An adaptive platform trial (APT) is a trial in which multiple treatments for the same disease are tested simultaneously. New interventions can be added or replace existing ones during the course of the trial in accordance with pre-specified criteria. APTs offer innovations that could reshape clinical trials, and several APTs are now funded in various disease areas. APTs enhance research efficiency, shorten the duration of futile studies, and optimise sample size and study duration based on emerging data. The platform design allows for subsequent levels of randomisation if further treatments require evaluation.

The initial randomisation ratio is fixed 1:1 for a comparison between two trial arms, but the trial has the capability for these proportions to be altered according to participants' responses to interventions. Pre-specified decision criteria allow for dropping a treatment for futility, declaring a treatment superior, or adding a new treatment to be tested. If at any point a treatment is deemed superior to the usual care arm, the superior treatment may replace the usual care arm as the new standard of care.

Unmet Clinical Need Acute Respiratory Infections (ARIs) are a leading cause of death worldwide and in Hong Kong. There is relatively little evidence for early pathology- or pathogen-specific treatments for suspected community-acquired ARI (scARI). Every year, winter crises and epidemics are such that hospital wards, and particularly intensive care facilities, are frequently overstretched. Even treatments with moderate impact on survival or on hospital resources could be worthwhile.

One important area where evidence is scant is the role for steroids in scARI requiring hospitalisation. Although many trials report benefits of using steroids that outweigh adverse events(AEs) in severe COVID and community-acquired pneumonia(CAP), the value in hospitalised patients with less severe disease, in scARI and early treatment (e.g. started in EDs) is unclear. Specifically, evidence for a safe role for early, low dose, short-course prednisolone to safely reduce excessive inflammation, progression to sepsis and mortality in adult patients with scARI is needed.

All patients will receive UC in the participating hospitals. Initially randomisation will be between two treatment arms:

Control Arm: Placebo Active Treatment Arm I: Prednisolone 30mg tablets administered once a day for five days.

Study Type

Interventional

Enrollment (Estimated)

1300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Queen Mary Hospital
        • Contact:
          • Miffy Hudson Lam, Bachelor
          • Phone Number: +852-55063028
          • Email: lly201@hku.hk
        • Contact:
        • Principal Investigator:
          • Timothy Hudson Rainer, Clinical Professor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Patients will be eligible for the study if ALL the following are present:

  1. Adults ≥18 years of age; AND
  2. scARI; AND
  3. Intended hospitalisation; AND
  4. No medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial

Exclusion Criteria:

Patients will be excluded if the treating clinician considers that the patient is not suitable for the trial.

Patients may be excluded if any ONE of the following are present:

  1. Vulnerable subjects (pregnancy; cognitively impaired; prisoners; students; umemployee; minorities);
  2. Cardiac arrest or post-cardiac arrest ROSC;
  3. Not expected to survive 3 days due to pre-existing chronic disease;
  4. Palliative (comfort) care
  5. Undergoing active cancer therapy;
  6. Neutropenia due to chemotherapy/malignancy (but not due to sepsis)
  7. Immunocompromised or being treated with immunotherapy
  8. Organ transplantation
  9. HIV and on HIV drugs (indinavir, atazanavir, nelfinavir, saquinavir, ritonavir)
  10. Recent Surgery (within one month)
  11. Dialysis (including CAPD)
  12. Diabetic ketoacidosis
  13. Acute asthma
  14. Recurrent chest infection,
  15. Cushing's or Addisonian's disease,
  16. Long term systemic steroid
  17. Long-term antibiotics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo + usual care
Placebo tablets administered once a day for five days.
Drug: Placebo
This a tablet identical to prednisolone.
Other Names:
  • Prednis
Active Comparator: Active Treatment I + usual care
Prednisolone 30mg tablets administered once a day for five days.
Drug: Prednisolone 30 mg
This is a glucocorticoid like cortisol used for its anti-inflammatory, immunosuppressive, anti-neoplastic and vasoconstrictive effects. It binds to the glucocorticoid receptor, inhibiting pro-inflammatory signals and promoting anti-inflammatory signals. It has a short duration of action as the half-life is 2.1-3.5 hours and 98% is eliminated in urine. On 21 June 1955 it was granted FDA approval.
Other Names:
  • Prednisolone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
30-day all-cause sepsis or all-cause mortality
Time Frame: Up to 30-days
The proportion of patients with all-cause sepsis or all-cause mortality
Up to 30-days
30-day Severe Adverse Events
Time Frame: Up to 30-days
The proportion of patients with an SAE
Up to 30-days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: Up to 30-days
The proportion of patients with mortality
Up to 30-days
Sepsis
Time Frame: Up to 30-days
The proportion of patients with sepsis
Up to 30-days
Length of Hospital Stay
Time Frame: Up to 30-days
Differentiation of median length of stay
Up to 30-days
Patient Satisfaction
Time Frame: Up to 30-days
Differentiation of median patient satisfaction score [Score:0 - 10]
Up to 30-days
Maximal WHO Clinical Progression Scale(WHO-CPS)
Time Frame: Up to 30-days

Differentiation of median maximal WHO-CPS hospitalised patients with scARI. [0 - not infected] Ambulatory mild disease

  1. Not hospitalised, asymptomatic, no limitation on activities, virus detected;
  2. Not hospitalised, symptomatic, independent
  3. Not hospitalised, limitation on activities, assistance required; Hospitalised moderate disease
  4. Hospitalised, not requiring supplemental oxygen;
  5. Hospitalised, requiring supplemental oxygen; Hospitalised severe disease
  6. Hospitalised, on oxygen by Non-invasive ventilation(NIV) or high flow;
  7. Hospitalised, intubation and mechanical ventilation
  8. Hospitalised, mechanical ventilation or vasopressors
  9. Hospitalised, mechanical ventilation, vasopressors, dialysis or Extracorporeal membrane oxygenation(ECMO);
  10. Death.
Up to 30-days
Cost-effectiveness analysis
Time Frame: 30-days

Cost-effectiveness comparison between the two groups. • Cost-effectiveness analysis measure is the total cost difference between treatment group and placebo group divided by total Quality-adjusted life year(QALY) difference between treatment group and placebo group;

• Total cost difference between treatment group and placebo group divided by difference in primary and secondary outcomes between treatment group and placebo group
30-days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Investigators

  • Principal Investigator: Timothy H Rainer, The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 23, 2024

Primary Completion (Estimated)

December 8, 2027

Study Completion (Estimated)

December 8, 2028

Study Registration Dates

First Submitted

June 14, 2024

First Submitted That Met QC Criteria

June 21, 2024

First Posted (Actual)

June 25, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 13, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PREDICATE

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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