Ignite Creation Date:
2024-07-17 @ 11:31 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06472219
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-25
First Post:
2024-06-14
Brief Title:
PREDICATE Trial For Respiratory Tract Infections
Sponsor:
The University of Hong Kong
Organization:
The University of Hong Kong
Study Overview
Official Title:
Early Prednisolone for Suspected Community-acquired Acute Respiratory Tract Infection PREDICATE A Double-blind Randomised Multi-centre Adaptive Platform Controlled Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 eventsSAEs not to exceed 5 between active treatment group and control
Benefits to Hong Kong and Worldwide Active treatments eg prednisolone are cheap HK02 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
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 eventsSAEs not to exceed 5 between active treatment group and control
Benefits to Hong Kong and Worldwide Active treatments eg prednisolone are cheap HK02 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
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 schoolwork 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 andor viral pathogen As many ARIs follow generic hyperinflammatory pathways evaluating and repurposing existing anti-inflammatory drugs eg 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 11 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 eventsAEs in severe COVID and community-acquired pneumoniaCAP the value in hospitalised patients with less severe disease in scARI and early treatment eg 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
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 schoolwork 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 andor viral pathogen As many ARIs follow generic hyperinflammatory pathways evaluating and repurposing existing anti-inflammatory drugs eg 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 11 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 eventsAEs in severe COVID and community-acquired pneumoniaCAP the value in hospitalised patients with less severe disease in scARI and early treatment eg 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None