| CTRI Number |
CTRI/2024/06/069529 [Registered on: 26/06/2024] Trial Registered Prospectively |
| Last Modified On: |
26/06/2024 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
To study effectiveness of treatment with colistin based triple antimicrobial combination therapy versus minocycline based triple antimicrobial combination therapy in critically ill patients infected with carbapenem resistant Acinetobacter baumanni |
|
Scientific Title of Study
|
Comparison of treatment failure with Minocycline versus Colistin Based Triple Antimicrobial Therapy for Carbapenem Resistant Acinetobacter Baumannii Infection in Critical Care Unit A Randomized Controlled Trial |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Pooja Bhardwaj |
| Designation |
Senior Resident |
| Affiliation |
AIIMS Rishikesh |
| Address |
Department of Anesthesiology,Block A, Level 6,AIIMS Rishikesh
Dehradun
UTTARANCHAL
249203
India |
| Phone |
8270278628 |
| Fax |
|
| Email |
bhardwajjpooja08@yahoo.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Pooja Bhardwaj |
| Designation |
student |
| Affiliation |
AIIMS Rishikesh |
| Address |
Department of Anesthesiology,Block A, Level 6,AIIMS Rishikesh
Dehradun
UTTARANCHAL
249203
India |
| Phone |
8270278628 |
| Fax |
|
| Email |
bhardwajjpooja08@yahoo.com |
|
Details of Contact Person
Public Query
|
| Name |
Pooja Bhardwaj |
| Designation |
Senior Resident |
| Affiliation |
AIIMS Rishikesh |
| Address |
Department of Anesthesiology,Block A, Level 6,AIIMS Rishikesh
Dehradun
UTTARANCHAL
249203
India |
| Phone |
8270278628 |
| Fax |
|
| Email |
bhardwajjpooja08@yahoo.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
NIL |
| Address |
NA |
| Type of Sponsor |
Other [NIL] |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Pooja Bhardwaj |
All India Institute of Medical Sciences,Rishikesh |
Critical Care Unit, Level 6, A Block ,AIIMS Rishikesh
Dehradun
UTTARANCHAL |
8270278628
bhardwajjpooja08@yahoo.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| All India Institute of Medical Sciences, Rishikesh, Institutional Ethics Committee Rishikesh Institutional Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: B968||Other specified bacterial agents as the cause of diseases classified elsewhere, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Colistin based triple antimicrobial combination therapy |
patients having blood cultures or respiratory tract specimen cultures (including semi-quantitative and/or quantitative cultures of sputum, bronchoalveolar lavage (BAL), endotracheal aspirate or pleural effusion) that grow MDR Acinetobacter baumannii, will be evaluated for potential participation in the study. Informed consent will be obtained from patient or legally authorized representative (LAR)prior to any further study activities. After obtaining written informed consent patients will be randomized to either the minocycline based combination group or the colistin based combination group.Colistin will be administered in the form of its intravenous prodrug, Colistimethate sodium. Colistin dose(9 million units as loading dose and then 4.5 million units q12h) will be diluted into 100 mL of normal saline and given twice a day infused as (IV) infusion over 1 hour.Meropenem 2gm will be given three times a day as intravenous infusion (over 3 hours) and Ampicillin Sulbactam 6gm will be given as intravenous infusion (over 4 hours) thrice a day in both the groups. Blood and sputum or endotracheal aspirate cultures will be obtained on the day 1,3,5,7,10,12th day or within 24 hours after the end of study therapy, unless microbiologic cure has already been demonstrated |
| Intervention |
Minocycline based triple antimicrobial combination therapy |
patients having blood cultures or respiratory tract specimen cultures (including semi-quantitative and/or quantitative cultures of sputum, bronchoalveolar lavage (BAL), endotracheal aspirate or pleural effusion) that grow MDR Acinetobacter baumannii, will be evaluated for potential participation in the study. Informed consent will be obtained from patient or legally authorized representative (LAR)prior to any further study activities. After obtaining written informed consent patients will be randomized to either the minocycline based combination group or the colistin based combination group.For loading dose in patients allotted to minocycline group, minocycline (200mg twice a day) will be loaded in syringe identical to colistin and infused over same time as loading dose of colistin and maintenance doses for both drugs will be given by reconstitution in 100 ml normal saline and both drugs will be loaded in identical syringes and given twice a day as (iv) infusion over 1 hour. Meropenem 2gm will be given three times a day as intravenous infusion (over 3 hours) and Ampicillin Sulbactam 6gm will be given as intravenous infusion (over 4 hours) thrice a day in both the groups. Blood and sputum or endotracheal aspirate cultures will be obtained on the day 1,3,5,7,10,12th day or within 24 hours after the end of study therapy, unless microbiologic cure has already been demonstrated. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
75.00 Year(s) |
| Gender |
Both |
| Details |
Patients admitted in critical care unit of our hospital having either a bloodstream infection (BSI) and/or pneumonia due to MDR carbapenem resistant Acinetobacter Baumanni
|
|
| ExclusionCriteria |
| Details |
Pregnant Patients,The presence of any of the following known clinical syndromes involving CRAB as a study pathogen which necessitate durations of antimicrobial therapies greater than 14 days: endocarditis, osteomyelitis, prosthetic joint infections, meningitis and/or other central nervous system infections.
Patients with known severe drug allergy to either of the study drugs or to β-lactams.
Patients with polymicrobial infections.
Refusal to participate in study.
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Comparison of treatment failure after anti-CRAB treatment between minocycline versus colistin based triple antimicrobial therapy for carbapenem resistant Acinetobacter Baumannii Infection in critical care unit for a duration specified by protocol |
3,5,7,10,12th day or within 24 hours after the end of study therapy |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Comparison of microbiological response, all-cause mortality after 28 days, change in SOFA score from baseline, duration of mechanical ventilation, duration of ICU stay, incidence of toxicities related to treatment medications between minocycline versus colistin based triple antimicrobial therapy for carbapenem resistant Acinetobacter Baumanni Infection in critical care unit |
3,5,7,10,12th day or within 24 hours after the end of study therapy |
|
|
Target Sample Size
|
Total Sample Size="100"
Sample Size from India="100"
Final Enrollment numbers achieved (Total)= "100"
Final Enrollment numbers achieved (India)="100" |
|
Phase of Trial
|
Phase 4 |
|
Date of First Enrollment (India)
|
01/08/2024 |
| Date of Study Completion (India) |
30/06/2025 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="1"
Months="6"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
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
|
Carbapenem resistant A. baumanni (CRAB)
was ranked number one priority for antibiotic research and development by
WHO. Rise in carbapenem resistance is leading
to increased usage of colistin, which eventually increases colistin
resistance. Current guidelines recommend combined antimicrobial
therapy for moderate to severe CRAB infection in ICU with high dose sulbactam
being a component of combination therapy even if in vitro resistance is
detected. The triple antibiotic combination regimen has shown clinical and in
vitro effectiveness in patients with CRAB infections(9).There is lack of
studies exploring effectiveness of non colistin based antibiotics combination therapies
for CRAB .Through this study we will try to compare effectiveness of non
colistin based combination therapy for CRAB infections thereby preventing
emergence of resistance to colistin. The primary aim of the study
is comparison
of treatment failure (defined as per protocol) with Minocycline
versus Colistin Based Triple Antimicrobial Therapy for Carbapenem Resistant
Acinetobacter Baumani Infection in Critical Care Unit |