| CTRI Number |
CTRI/2024/04/066197 [Registered on: 24/04/2024] Trial Registered Prospectively |
| Last Modified On: |
15/04/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Diagnostic |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
Impact of Rapid Diagnostics using a FilmArray Test and Early Targeted Treatment with Ceftazidime-Avibactam for Management of Severe Infections: A Comparative Study Against Standard Care |
|
Scientific Title of Study
|
Early impact therapy with ceftazidime-avibactam via rapid diagnostics versus standard of care antibiotics and diagnostics in patients with bloodstream infection, hospital-acquired pneumonia or ventilator-associated pneumonia due to Pseudomonas aeruginosa or carbapenemase producing Enterobacterales |
| Trial Acronym |
RAPID |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NCT05979545 |
ClinicalTrials.gov |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr George M Varghese |
| Designation |
Professor |
| Affiliation |
Christian Medical College Vellore |
| Address |
Department of Infectious Diseases,
Christian Medical College,
Ida Scudder Road,
Vellore
TAMIL NADU
India.
Vellore
TAMIL NADU
632004
India |
| Phone |
9487393015 |
| Fax |
|
| Email |
georgemvarghese@hotmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr George M Varghese |
| Designation |
Professor |
| Affiliation |
Christian Medical College Vellore |
| Address |
Department of Infectious Diseases,
Christian Medical College,
Ida Scudder Road,
Vellore
TAMIL NADU
India.
TAMIL NADU
632004
India |
| Phone |
9487393015 |
| Fax |
|
| Email |
georgemvarghese@hotmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr George M Varghese |
| Designation |
Professor |
| Affiliation |
Christian Medical College Vellore |
| Address |
Department of Infectious Diseases,
Christian Medical College,
Ida Scudder Road,
Vellore
TAMIL NADU
India.
TAMIL NADU
632004
India |
| Phone |
9487393015 |
| Fax |
|
| Email |
georgemvarghese@hotmail.com |
|
|
Source of Monetary or Material Support
|
| ADVANCE-ID,
Saw swee hock School of Public Health,
National University of Singapore
21 Lower Kent Ridge Road
Singapore 119077 |
|
|
Primary Sponsor
|
| Name |
ADVANCE ID |
| Address |
ADVANCE-ID,
Saw swee hock School of Public Health,
National University of Singapore
21 Lower Kent Ridge Road
Singapore 119077 |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
Italy
Malaysia
Republic of Korea
Thailand
India
Taiwan
Turkey |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr George M Varghese |
Christian Medical College |
Deaprtment of Infectious Diseases, Christian Medical College, Ida Scudder Road, Vellore
Vellore
TAMIL NADU |
9487393015
georgemvarghese@hotmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| CHRISTIAN MEDICAL COLLEGE,VELLORE |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: B965||Pseudomonas (aeruginosa) (mallei)(pseudomallei) as the cause of diseases classified elsewhere, (2) ICD-10 Condition: B961||Klebsiella pneumoniae [K. pneumoniae] as the cause of diseases classified elsewhere, (3) ICD-10 Condition: B962||Escherichia coli [E. coli ] as thecause of diseases classified elsewhere, (4) ICD-10 Condition: B968||Other specified bacterial agents as the cause of diseases classified elsewhere, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Rapid diagnosis using BioFire FilmArray and targeted therapy using Ceftazidime-avibactam |
Patients randomised to the intervention arm, will have the BioFire Blood Culture Identification 2 Panel (BCID2) used for positive blood cultures and/or the BioFire FilmArray Pneumonia plus Panel for respiratory tract specimens if having hospital-acquired pneumonia or ventilator-associated pneumonia. Standard of care diagnostics will also be used. Antibiotic guidelines will be provided to clinicians to aid interpretation of test results and treatment prescription. Ceftazidime-avibactam will be available for targeted use in patients with Pseudomonas aeruginosa or carbapenemase producing Enterobacterales with or without aztreonam.The standard dose of ceftazidime-avibactam for adults will be 2000mg/500mg every 8 hours given intravenously over 2 hours. Dose-adjust for creatinine clearance (CrCl) as follows: 1000 mg/250 mg every 8 hours for CrCl more than 30 to ≤50 mL/min, 750mg/187.5mg every 12 hours for CrCl more than 15 to ≤30 mL/min, 750mg/187.5mg every 24 hours CrCl more than 5 to ≤15 mL/min and 750mg/187.5mg every 48 hours for ESRD including haemodialysis (should be administered after dialysis).The standard dose of aztreonam will be 2 g IV q8h, infused over 2 hours; Dose-adjust for creatinine clearance (CrCl) as follows: CrCl more than 30 mL/min no adjustment, 10-30 mL/min: 2 g loading dose, then 1g every 8 hourly, CrCl less than 10 mL/min: 2 g loading dose, then 500mg every 8 hourly.
|
| Comparator Agent |
Standard of Care |
Patients randomised to the control arm, will have samples analysed by clinical microbiology laboratories using standard of care diagnostics.
Antibiotics will be available to these patients as per usual institutional practice. Patients may receive ceftazidime-avibactam according to local antimicrobial stewardship guidelines but will receive this antibiotic from hospital supplies. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
a) At risk of bloodstream infections, hospital-acquired pneumonia or ventilator-associated pneumonia due to Pseudomonas aeruginosa or carbapenemase producing Enterobacterales; OR,
b) whose blood culture bottles growing Gram negative bacilli; OR,
c) who are suspected to have hospital-acquired pneumonia or ventilator-associated pneumonia and whose respiratory samples show Gram negative bacteria on Gram stain
|
|
| ExclusionCriteria |
| Details |
a) Refractory shock or comorbid condition such that patient not expected to survive more than 48 hours; OR,
b) where the bloodstream infection is thought to be related to a vascular catheter and the catheter is unable to be removed; OR,
c) treatment is not with the intent to cure the infection; OR,
d) patients previously randomised in this trial within the last 60 days. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
Primary outcome is a composite measure in which any of the following occur:
Patient has died from any cause; OR,
SOFA score has not improved at Day 14 compared with baseline score on day of collection of index respiratory culture
Modified SOFA will be used, if the full SOFA score cannot be calculated e.g. outside of the intensive care unit setting. If the study participant is discharged with improved clinical status prior to day 14, it will be assumed that SOFA score has improved. If the study participant is discharged with expected demise, it will be assumed that SOFA score has failed to improve. |
within 14 days from collection of index blood culture/respiratory culture |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Clinical response as determined retrospectively by an adjudication committee
|
Day 7 and Day 14 post index culture |
All-cause mortality
|
Day 14, Day 28 and Day 60 post index culture |
| Days alive and out of hospital. |
28 days from the date of index culture |
Length of stay in ICU.
|
28 days from date of index culture. |
Length of stay in hospital.
|
28 days from date of index culture. |
Type of accommodation on discharge from hospital
|
date of discharge |
| Duration of mechanical ventilation |
28 days from date of index culture |
Persistence of bacteremia
|
day 4 from date of index culture |
Persistence of microbiologic growth of at least one organism growing from index respiratory culture
|
day 7 from date of index respiratory culture |
| Development of resistance to meropenem, colistin or ceftazidime-avibactam in any bacteria grown from clinically-indicated cultures |
28 days from date of index culture |
| Development of acute kidney injury (KDIGO definitions). |
28 days from date of index culture |
| Development of Clostridioides difficile diarrhea. |
28 days from date of index culture |
Time from index culture sample received by the laboratory to antibiotic therapy active in vitro (in hours)
|
from date of index culture |
Number of days on antibiotics(total, and by antibiotic type)
|
in 28 days of index culture collection |
| Percentage of patients undergoing modification of antibiotic therapy |
7 days after microbiology diagnostics for the index culture |
Time to detection of carbapenem resistance (in hours)
|
from index culture sample received by the laboratory |
Time to detection of resistance to ceftriaxone/cefotaxime (in hours)
|
from index culture sample received by the laboratory |
| Time to detection of Acinetobacter baumannii calcoaceitcus complex or Stenotrophomonas maltophilia (in hours) |
from index culture sample received by the laboratory |
| Functional outcome |
at Day 14, Day 28 and Day 60 from collection of index culture |
| Composite outcome measure defined by Desirability of Outcome Ranking (DOOR) |
at Day 28 from index culture sample |
|
|
Target Sample Size
|
Total Sample Size="5900"
Sample Size from India="600"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 4 |
|
Date of First Enrollment (India)
|
01/06/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
26/12/2023 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="2"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Antimicrobial resistance is a growing public health threat and the key strategy to reduce mortality is to improve diagnostics and initiate early targeted antibiotic therapies. Conventional diagnostic methods take 3-5 days for bacterial identification and susceptibility tests. Rapid diagnostics detect associated antimicrobial resistance within hours and hence enabling early treatment. Though validated against EUCAST and CLSI standards, assimilation to routine clinical care is slow mainly due to the inadequate evidence to support the benefits of rapid diagnostics. The RAPID trial proposes a seamless intervention linking rapid bacterial isolate identification and antibiotic resistance gene detection and targeted antibiotic prescription to minimise time between infection onset and appropriate treatment. The primary hypothesis is the study interventions will lead to improved clinical outcomes compared to standard antibiotic susceptibility testing and treatment. This study is an open labelled non blinded randomised control trial. The primary study population will consist of patients with Pseudomonas aeruginosa or carbapenemase producing Enterobacterales bloodstream infections, hospital-acquired pneumonia and ventilator-associated pneumonia. Patients will be randomised to either a control or intervention arm. Patients randomised to the intervention arm will have relevant specimens analysed by rapid microbiological diagnostics and will have early availability of ceftazidime-avibactam with or without aztreonam if appropriate. Patients in the control arm will undergo routine standard of care diagnostics and treatment in accordance to the institutional policies as decided by the treating physician. |