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CTRI Number  CTRI/2023/10/058663 [Registered on: 13/10/2023] Trial Registered Prospectively
Last Modified On: 05/10/2023
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Preventive 
Study Design  Non-randomized, Multiple Arm Trial 
Public Title of Study   A clinical trial to study the cardioprotective effect of remote ischemic preconditioning in acute coronary syndrome patients  
Scientific Title of Study   Evaluation of the cardioprotective effect of remote ischaemic preconditioning in acute coronary syndrome patients and its correlation with vitamin D 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Harlokesh Narayan Yadav 
Designation  Additional Professor 
Affiliation  All Institute of Medical Sciences New Delhi 
Address  Room no 5006 Convergence block AIIMS New Delhi

South West
DELHI
110029
India 
Phone    
Fax    
Email  hnyadav@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Harlokesh Narayan Yadav 
Designation  Additional Professor 
Affiliation  All Institute of Medical Sciences New Delhi 
Address  Room no 5006 Convergence block AIIMS New Delhi

South West
DELHI
110029
India 
Phone    
Fax    
Email  hnyadav@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Harlokesh Narayan Yadav 
Designation  Additional Professor 
Affiliation  All Institute of Medical Sciences New Delhi 
Address  Room no 5006 Convergence block AIIMS New Delhi

South West
DELHI
110029
India 
Phone    
Fax    
Email  hnyadav@gmail.com  
 
Source of Monetary or Material Support  
Department of Health Research, Red Cross Road,New Delhi,Delhi, Gokul Nagar, Sansad Marg Area, New Delhi, Delhi 110001 
 
Primary Sponsor  
Name  Department of Health Research 
Address  Department of Health Research IRCS Building 2nd Floor Red Cross Road New Delhi 110001 
Type of Sponsor  Government funding agency 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Harlokesh Nrayan Yadav  AIIMS New Delhi  Department of Emergency Medicine AIIMS New Delhi
South West
DELHI 
8171544655

hnyadav@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institute Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: I228||Subsequent ST elevation (STEMI) myocardial infarction of other sites,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Remote ischemic preconditioning  ● At the time of enrolment blood samples will be taken from the patients and divided into three groups based on vitamin D levels (vitamin D levels ≤10 (deficient), 10-29 (insufficient) and ≥30 ng/ml (normal). ● 20 minutes before the Percutaneous coronary intervention(PCI) patients will be given remote ischemic preconditioning where an automated cuff will be placed on the upper arm and inflated to more than 20 mm Hg of systolic pressure for 5 min and then deflated for 5 min, a cycle which will be programmed to be undertaken 4 times in total. All patients will complete the 4 cycles (that is widely used in various clinical setups in different countries (García Del Blanco et al., 2021; Lamidi et al., 2021; Mohammad Seyedsaadat et al., 2019; Zarbock et al., 2015) ● The blood samples will be taken before and after 24 hrs of PCI for evaluating cardiac injury markers and inflammatory markers. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  90.00 Year(s)
Gender  Both 
Details  (1) All ACS patients with STEMI/NSTEMI enrolled for stent implantation
(2) Age > 18 years.
(3) Gender: Both M and F 
 
ExclusionCriteria 
Details  (1) Patients below 18 years
(2) Coronary artery bypass grafting (CABG) patients
(3) Patients with permanent pacemaker
(4) Patients with a Left Bundle Branch block on electrocardiogram
(5) Patients with cardiogenic shock
(6) Breastfeeding or pregnant women 
 
Method of Generating Random Sequence   Not Applicable 
Method of Concealment   Not Applicable 
Blinding/Masking   Not Applicable 
Primary Outcome  
Outcome  TimePoints 
Difference in the levels of cardiac biomarkers, inflammatory markers (IL-6, IL-8, IL-10, IL-33, CRP, IFN gamma) and vitamin D before and 24 hours after PCI in control and RIPC arm.   At the time of enrolment and 24 hours post PCI.  
 
Secondary Outcome  
Outcome  TimePoints 
Comparison of the following outcomes between the RIPC & control arm:
1. Difference in survival at 30 days
2. Difference in non-fatal MACE at 30 day
3. Measurement of Ejection fraction, end diastolic volume, end systolic volume, WMSI, RWMA at 30 days following primary PCI
 
30 days after enrollment  
 
Target Sample Size   Total Sample Size="180"
Sample Size from India="180" 
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)   20/10/2023 
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="3"
Months="0"
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  
Acute coronary syndrome (ACS) is an emergency condition where timely reperfusion therapy would
help to save the infarct size. Remote ischemic preconditioning (RIPC) has been put forward as a
promising cardioprotective strategy for patients with ischemic heart disease (IHD) that involves the
induction of brief and intermittent cycles of ischemia and reperfusion in a distant organ (Pryds et al.,
2019). Different endogenous substances like adenosine, bradykinin and calcitonin gene-related peptide
(CGRP) which have been reported to produce cardioprotection during I/R injury are released during
preconditioning (Hausenloy DJ et al. 2008). The substances generated in the remote organ during RIPC may pass via the blood and upon reaching the myocardium activate intracellular signalling pathways.
These may include adenosine, erythropoietin, MicroRNAs, Nitrite, CGRP, apolipoprotein A1, amino
acids, glucagon-like peptide and extracellular vesicles (Billah et al., 2019). Several clinical reports have
revealed that RIPC (prior, during, or following myocardial reperfusion) can reduce the myocardial
infarct size, increase myocardial salvage, and prevent clinical adverse events happening in patients
(Stiermaier et al., 2019). In India studies done by Sundeep et al., 2015 have shown that RIPC, leads to
a significant reduction in the incidence of PCI-related MI. Another study by Suresh et al., 2020 have
shown that PCI in patients with ACS could provide protection against ischemia-reperfusion injury.
However, the studies related to the cardioprotective effect of RIPC have come up with conflicting
results. In one of the studies , it showed that RIPC did not reduce troponin release, improve
hemodynamics, or enhance organ protection (Rahman et al., 2010). A study conducted by Prasad A et
al. 2013 did not support an adjunctive role for remote IP in low- to moderate-risk patients undergoing
percutaneous coronary intervention (PCI). It had been observed that remote ischemic preconditioning
did not reduce myocardial or kidney injury during cardiac surgery and this type of therapy is unlikely
to substantially improve patient- important outcomes in cardiac surgery (Walsh M et al. 2016).
Vitamin D, on the other hand, is known to be a major cause of IHD and is a prevailing global health
concern. Low vitamin D levels have been linked to an increased risk of myocardial infarction (MI),
stroke, CVD mortality, and heart failure in case-control and other prospective epidemiologic studies
(Kheiri et al., 2018). An I/R injury model was induced by left coronary artery ligation in Sprague-
Dawley rats (in vivo) and Langendorff perfusion of isolated hearts (in vitro). It demonstrates that
vitamin D plays a protective role against myocardial injury by inhibiting inflammation through
repressing the RhoA/ROCK/NF-κB pathway (Qian X et al.2019). It was demonstrated that treatment of
vitamin D markedly improved left ventricular function (LVF) in mice, and reduced plasma level of cTn-
I as a marker of cardiac injury. Moreover, the effects of vitamin D was associated with attenuations in
both chemokine and cytokines expression following I/R, that accompanied by down-regulation of
activation of ERK1-2 pathway (Yousif NG et al.2017). There have been various previous clinical
studies which have shown the protective effect of vitamin D on I/R injury by maintaining the ejection
fraction and limiting the infarct size which may help in decreasing the morbidity and mortality in the
population. Furthermore, it has been reported that vitamin D administration in people suffering from
IHD confers cardioprotection in terms of decreased cardiac injury markers i.e. troponin, CK-MB and
decrease the release of inflammatory markers (IL 6, IL 8, IL 10, IL-33, CRP, interferon (IFN)-γ).
Therefore, here the question arises if vitamin D supplementation shows a protective effect in I/R injury
during coronary intervention; does that mean that vitamin D deficient people are more prone to I/R
injury? Moreover, if preconditioning is given in vitamin D deficient patients will it compromise the
cardioprotective effect of pre-conditioning. Although there is evidence that vitamin D is associated with
heart disease, however, no information is available regarding 25- hydroxyvitamin D3 (Vit D) and remote ischemic preconditioning (RIPC). Furthermore, literature reports that the cardioprotective effect
of preconditioning shows diversity from person to person with some being non-responsive so does that
mean those people would be vitamin D deficient. Therefore, the present study has been designed to
evaluate the cardioprotective effect of remote ischemic preconditioning in ACS patients and correlate
it with serum vitamin D levels.
 
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