| CTRI Number |
CTRI/2023/11/059832 [Registered on: 14/11/2023] Trial Registered Prospectively |
| Last Modified On: |
18/12/2024 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Comparison of the safety and efficacy of empirical use of colistin monotherapy versus colistin plus minocycline combination therapy in ventilator associated pneumonia(VAP) due to carbapenem resistant gram negative organism infection - a randomized controlled trial |
|
Scientific Title of Study
|
Comparison of the safety and efficacy of empirical use of colistin monotherapy versus colistin plus minocycline combination therapy in ventilator associated pneumonia(VAP) due to carbapenem resistant gram negative organism infection - 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 |
Prof Samir Malhotra |
| Designation |
Professor and Head |
| Affiliation |
PGIMER Chandigarh |
| Address |
Department of Pharmacology, PGIMER, Chandigarh
Chandigarh
CHANDIGARH
160012
India |
| Phone |
9417016343 |
| Fax |
|
| Email |
smal.pgi@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Prof Samir Malhotra |
| Designation |
Professor and Head |
| Affiliation |
PGIMER Chandigarh |
| Address |
Department of Pharmacology, PGIMER, Chandigarh
Chandigarh
CHANDIGARH
160012
India |
| Phone |
9417016343 |
| Fax |
|
| Email |
smal.pgi@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Amol |
| Designation |
DM resident |
| Affiliation |
PGIMER Chandigarh |
| Address |
Department of Pharmacology, PGIMER, Chandigarh
Department of Pharmacology, PGIMER, Chandigarh
Chandigarh
CHANDIGARH
160012
India |
| Phone |
9990245973 |
| Fax |
|
| Email |
seeamol83@gmail.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
Prof Samir Malhotra |
| Address |
Department of Pharmacology, PGIMER, Chandigarh |
| Type of Sponsor |
Other [Self] |
|
|
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 Amol N Patil |
PGIMER Chandigarh Hospital |
Room No 4012, Department of Pharmacology, Research block B, PGIMER
Sector 12
Chandigarh
Chandigarh
CHANDIGARH |
9990245973
seeamol83@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| PGIMER |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: A415||Sepsis due to other Gram-negativeorganisms, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Colistin monotherapy |
Intravenous colistin
a loading dose of 9 million international units (MIU) of colistin followed by a maintenance dose of 4.5 MIU every 12 h
Plus
Colistin Nebulization
Aerosolized form: 2.5 million U q12h diluted in 4 mL normal saline delivered via nebulizer (jet or ultrasonic)
|
| Intervention |
Colistin plus minocycline combination therapy |
Intravenous colistin
a loading dose of 9 million international units (MIU) of colistin followed by a maintenance dose of 4.5 MIU every 12 h
Plus
Colistin Nebulization
Aerosolized form: 2.5 million U q12h diluted in 4 mL normal saline delivered via nebulizer (jet or ultrasonic)
Plus
Intravenous minocycline
200 mg PO/IV initially, then 100 mg PO/IV q12hr;
|
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
95.00 Year(s) |
| Gender |
Both |
| Details |
1. Hospitalized and receiving mechanical ventilation for at least 48 hours at the time of study enrolment
2. Patient with VAP diagnosis as per hospital protocol definition#
3. Endotracheal aspirate sample sent for culture and sensitivity prior to study drug initiation.
4. Legally acceptable representative(LAR) providing informed consent, and willing to give follow up |
|
| ExclusionCriteria |
| Details |
1. History of hypersensitivity to any of the two antimicrobials of the study (colistin/ minocycline).
2. Received colistin/polymyxins therapy or minocycline for a minimum time period of 72 hours within 96 hours prior to randomization
3. Renal insufficiency. [eGFR < 30%]
4. Patients included in another clinical trial in the past three months.
5. Pregnant or nursing woman
6. Patients with neutropenia (WBC < 500 cells/mm3)
7. Presence of primary infection at other sites, e.g., osteomyelitis, endocarditis, prosthetic joint infection, meningitis, or central nervous system infection
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Participant, Investigator and Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To compare the mortality rate in both the study groups |
Day 0, day 3, Day 7, Day 10, Day 14, and Day 28 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
To compare two study groups for-
A] Adverse events
B] Proportion of patients with clinical failure
C] Duration of hospitalization
D] Duration of Intensive Care Unit(ICU) stay,
E] Days on ventilator
F] Microbiological clearance of culture-proven organisms
g] Organism specific treatment response
|
Day 0, day 3, Day 7, Day 10, Day 14, and Day 28 |
|
|
Target Sample Size
|
Total Sample Size="200"
Sample Size from India="200"
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 3/ Phase 4 |
|
Date of First Enrollment (India)
|
27/11/2023 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| 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)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
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
|
Colistin resistance is an emerging issue in gram-negative bacterial infections, especially in ventilator-associated pneumonia(VAP) patients. Indian hospitals many a time need to start antimicrobial therapy empirically i.e. before a culture sensitivity report is available. The mortality rate at tertiary care referral hospitals is close to 50 % due to sepsis and compromised oxygen saturation. To find the best regimen, we are planning a single-centre, two-arm, prospective, double-blind, parallel-group, randomized controlled trial comparing the efficacy and safety of colistin monotherapy versus colistin plus minocycline combination therapy. It will be addressed in a randomized controlled trial manner by using computer-generated randomization codes. The outcome assessment will be blinded. It will happen at the end of two years by studying 200 patients at the ICUs of the Department of Internal Medicine, Pulmonology, PGIMER Chandigarh. The study will randomly allocate the VAP[ both clinical diagnosis & Lab confirmed] patients into monotherapy and combination therapy arms with other background medications. The clinician in charge can taper the antimicrobial therapy as per clinical and laboratory responses. Patients will be followed up during their hospital stay and till day 28 of study medication initiation. We will assess the 28 mortality in both arms besides other secondary endpoints like time on ventilator, duration of ICU and hospital stay, microbiological clearance, and adverse events. |