| CTRI Number |
CTRI/2024/09/074220 [Registered on: 24/09/2024] Trial Registered Prospectively |
| Last Modified On: |
12/09/2024 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Study to assess the benefits of Ivabradine in controlling heart rate and improving survival in patients with septic shock |
|
Scientific Title of Study
|
Effectiveness Of Enteral Ivabradine Plus
Standard Therapy Versus
Standard Therapy Alone For Heart Rate Control In Patients With Septic Shock : A Single Blind RCT |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Chackappen D Aymanom |
| Designation |
Senior Resident General Medicine |
| Affiliation |
All India Institute Of Medical Sciences Rishikesh |
| Address |
Chackappen D Aymanom
Department of General Medicine
Division of Hospital Medicine & Critical Care,
Level-6, Block -A, Room no- 016401
AIIMS RISHIKESH
UTTARAKHAND
Dehradun
UTTARANCHAL
249203
India |
| Phone |
8086113572 |
| Fax |
|
| Email |
chackappen@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Mukesh Bairwa |
| Designation |
Associate professor |
| Affiliation |
AIIMS RISHIKESH |
| Address |
Department of general medicine, Level 6, Block A, AIMS RISHIKESH
Dehradun
UTTARANCHAL
249203
India |
| Phone |
8130023989 |
| Fax |
|
| Email |
drmukeshbairwa1982@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Chackappen D Aymanom |
| Designation |
Senior Resident General Medicine |
| Affiliation |
All India Institute Of Medical Sciences Rishikesh |
| Address |
Chackappen D Aymanom
Department of General Medicine
Division of Hospital Medicine & Critical Care,
Level-6, Block -A, Room no- 016401
AIIMS RISHIKESH
UTTARAKHAND
Dehradun
UTTARANCHAL
249203
India |
| Phone |
8086113572 |
| Fax |
|
| Email |
chackappen@gmail.com |
|
|
Source of Monetary or Material Support
|
| All India Institute Of Medical Sciences Rishikesh
Rishikesh, Uttarakhand
Pin 249203 |
|
|
Primary Sponsor
|
| Name |
Chackappen D Aymanom |
| Address |
Chackappen D Aymanom
Senior Resident General Medicine
AIIMS Rishikesh
Pin 249203 |
| Type of Sponsor |
Government medical college |
|
|
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 Chackappen D Aymanom |
AIIMS RISHIKESH |
Department of General medicine, Division of Hospital Medicine and critical care, Medicine ICU, level 4, Block C2, Room no-034201 , Dehradun, Uttarakhand
Dehradun
UTTARANCHAL |
8086113572
chackappen@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional ethics committee AIIMS Rishikesh |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: R652||Severe sepsis, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Ivabradine plus standard therapy for septic shock |
Patients in the intervention group were administered 5 mg of Ivabradine, either orally or crushed and delivered via a feeding tube (preferably with feed), once daily for the first 24 hours following enrolment. If the target heart rate of less than 100 beats per minute was not achieved after 24 hours, the dose was increased by 2.5 mg every 12 hourly to a maximum dose of 7.5 mg twice daily, administered orally or via feeding tube. Heart rate was assessed prior to each dose.
Once the heart rate dropped below 90 beats per minute, the dose was reduced by 2.5 mg. Ivabradine was continued for 96 hours following the initiation of therapy. Beyond this period, the decision to continue Ivabradine was left to the discretion of the treating intensivist.
Ivabradine was discontinued if the noradrenaline requirement increased to more than 0.5 ug/kg/ min, or if the noradrenaline requirement persistently increased by more than 0.1 ug/kg/min from baseline for over 12 hours following the initiation of Ivabradine. In cases where a patient developed severe symptomatic bradycardia (heart rate less than 60 beats per minute with worsening hypotension), an intravenous isoprenaline infusion
(0.1-0.5 g/kg/min) was started, and Ivabradine was discontinued.
Isoprenaline was gradually tapered and stopped once the heart rate exceeded 70 beats per minute. |
| Comparator Agent |
Standard therapy for septic shock |
Patients with septic shock will receive standard care, including fluid resuscitation, vasopressor support, and other treatments as per ICU protocol, without Ivabradine. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
80.00 Year(s) |
| Gender |
Both |
| Details |
1. Septic shock diagnosed within 24 hours (Patients with heart rate more than 100 beats per minute and requiring noradrenaline support of 0.02-0.4 mcg/kg/min to maintain mean arterial pressure (MAP) above 65 mmHg despite adequate volume resuscitation)
2. Written informed consent |
|
| ExclusionCriteria |
| Details |
1. Patients less than 18 years or more than 80 years of age.
2. Pre-existing cardiovascular disease (coronary artery disease, congestive heart failure, cardiac rhythm abnormalities, conduction defects, congenital heart disease, or pacemaker in situ, post-cardiac arrest patients).
3. Patients with a history of pre-existing chronic renal failure with a glomerular filtration rate less than 15 mL/min.
4. Severe hepatic insufficiency (Model for End-Stage Liver Disease (MELD) score more than
30, serum bilirubin more than 2.5 times upper limit of normal (ULN), or serum transaminases more than five times ULN).
5. Pregnant or lactating patients.
6. Patients with hemoglobin less than 7 g/dL.
7. Patients with any contraindication to enteral drug administration (including patients with gastrointestinal perforation, mechanical bowel obstruction, or bowel ischemia).
8. Use of potent cytochrome P450 3A4 inhibitors such as azole-type antifungals (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, erythromycin), or HIV protease inhibitors (nelfinavir, ritonavir).
9. Patients with hyperthyroidism.
10. Patients with a baseline heart rate less than 70 beats per minute. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Participant Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
1. Difference in heart rate between the two groups during the first 96 hours after enrolment
|
Time points for assessing the heart rate are:
1. At enrolment
2. At 24 hours
3. At 48 hours
4. At 96 hours
These measurements will be recorded over the course of the 18-month trial period.
|
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Effect of IVABRADINE on 14 day Mortality |
14 days |
| Effect of Ivabradine on Mean arterial pressure |
Time points for assessing
1.At enrolment
2. At 24 hours
3. At 48 hours
4. At 96 hours |
| Effect of IVABRADINE on 24 hour urine output |
24 hours |
Effect of IVABRADINE on severity of sepsis assessed by following parameters
Serum lactate levels, SOFA score,PaO2/FiO2 , SCvO2,GCS |
Time points for assessing are:
1. At enrolment
2. At 24 hours
3. At 48 hours
4. At 96 hours |
| Length of ICU STAY |
Total length of ICU stay in days |
| Effect of IVABRADINE on vasopressor ( Noradrenaline dose in mcg/kg/min) use |
Time points for assessing are:
1. At enrolment
2. At 24 hours
3. At 48 hours
4. At 96 hours |
| Effect of IVABRADINE on ejection fraction |
Time points for assessing are:
1. At enrolment
2. At 24 hours
3. At 48 hours
4. At 96 hours |
|
|
Target Sample Size
|
Total Sample Size="234"
Sample Size from India="234"
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
|
N/A |
|
Date of First Enrollment (India)
|
24/09/2024 |
| 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="1"
Months="6"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| 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
|
"Effectiveness of Enteral Ivabradine Plus Standard Therapy Versus Standard Therapy Alone for Heart Rate Control in Patients with Septic Shock: A Single Blind RCT," is designed to evaluate whether the addition of Ivabradine to standard therapy improves heart rate control in patients with septic shock. The study will recruit a total of 234 participants, with 117 in each arm, accounting for a 10% loss to follow-up. Participants will be randomly assigned to receive either Ivabradine plus standard therapy or standard therapy alone. Heart rate will be measured at baseline, 24 hours, 48 hours, 96 hours, and prior to each dose of Ivabradine. Hypothesis: The study hypothesizes that Ivabradine plus standard therapy will result in superior heart rate control compared to standard therapy alone in patients with septic shock.
The primary outcome of the study is heart rate control at the specified time points. The goal is to determine if Ivabradine more effectively reduces heart rate compared to standard therapy alone in the context of septic shock. Secondary outcomes include evaluating clinical parameters such as overall hemodynamic stability, requirement of additional vasopressors, duration of mechanical ventilation, ICU length of stay, and mortality rates. These secondary outcomes will provide a broader understanding of Ivabradine’s potential impact on patient outcomes beyond heart rate control, contributing to overall management strategies for septic shock. The purpose of this study is to explore the potential benefits of Ivabradine in reducing heart rate in septic shock patients, a critical aspect of hemodynamic management. By investigating the effect of Ivabradine in this specific patient population, the trial aims to provide valuable insights that could lead to improved therapeutic strategies for managing septic shock, potentially improving clinical outcomes and patient survival. There is limited evidence. Considering the Indian scenario most studies are observational studies producing conflicting results. RCT it considered the second evidence in evidence-based medicine, and considering the amount of patients in septic shock, this study is the need of hour. |