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CTRI Number  CTRI/2024/07/071135 [Registered on: 23/07/2024] Trial Registered Prospectively
Last Modified On: 30/12/2024
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Drug
Preventive 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   A clinical trial to study the effect of melatonin in prevention of postoperative delirium in patients undergoing bypass surgeries for chronic limb ischaemia. 
Scientific Title of Study   A placebo controlled double-blind randomized clinical trial to study the effect of melatonin in prevention of post-operative delirium in patients undergoing reperfusion surgery for chronic limb ischaemia. 
Trial Acronym  nil 
Secondary IDs if Any  
Secondary ID  Identifier 
Nil  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Basudev Pati 
Designation  Junior resident academic 
Affiliation  PGIMER, Chandigarh 
Address  Post graduate institute of medical education and research, sector 12, Chandigarh, India

Chandigarh
CHANDIGARH
160012
India 
Phone  09439661990  
Fax    
Email  basudevpati738@gmail.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Sanjay Kumar Jaswal 
Designation  Assistant professor 
Affiliation  PGIMER,Chandigarh 
Address  Post graduate institute of medical education and research, sector 12, Chandigarh, India

Chandigarh
CHANDIGARH
160012
India 
Phone  09779170944  
Fax    
Email  sanjayjaswal247@gmail.com  
 
Details of Contact Person
Public Query  
Name  Dr Sanjay Kumar Jaswal 
Designation  Assistant professor 
Affiliation  PGIMER,Chandigarh 
Address  Post graduate institute of medical education and research, sector 12, Chandigarh, India

Chandigarh
CHANDIGARH
160012
India 
Phone  09779170944  
Fax    
Email  sanjayjaswal247@gmail.com  
 
Source of Monetary or Material Support  
Department of Anaesthesia and Intensive Care, Post graduate institute of medical education and research sector 12,Chandigarh, India PIN-160012 
 
Primary Sponsor  
Name  Dr Basudev Pati 
Address  Department of Anaesthesia and Intensive Care, Post graduate institute of medical education and research sector 12,Chandigarh 
Type of Sponsor  Other [self sponsored] 
 
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 Basudev Pati  Post graduate institute of medical education and research  Department of Anaesthesia and Intensive care general surgery OT 4th floor Nehru hospital extension
Chandigarh
CHANDIGARH 		 09439661990

basudevpati738@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
POST GRADUATE INSTITUTE OF MEDICAL EDUCATION AND RESEARCH CHANDIGARH INSTITUIONAL ETHICS COMMITTEE(INTRAMURAL)  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: I739||Peripheral vascular disease, unspecified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Melatonin  Patient will receive melatonin 3mg on two consecutive evenings, on the evening before surgery and one day prior to the day before surgery (at seven p.m.). 
Comparator Agent  placebo(vitamin B6 10 mg)  Patient will receive placebo on two consecutive evenings, on the evening before surgery and one day prior to the day before surgery (at seven p.m.). 
 
Inclusion Criteria  
Age From  40.00 Year(s)
Age To  75.00 Year(s)
Gender  Both 
Details  All patients in the age group of 40 to 75 years of age undergoing reperfusion surgery or bypass procedure for chronic limb ischaemia. The bypass procedure could be aorto-femoral, femoro-popliteal or aorto-femoro-popliteal bypass. 
 
ExclusionCriteria 
Details  Patients with known psychiatric disorders.
Pychotropic drugs consumption.
Patients on anticonvulsants.
History of ongoing substance abuse.
Severe anemia.
Severe copd or asthma.
CKD stage 3 and above.
History of cerebrovascular disease.
Sensory disorders including blindness,hearing loss, cognitive disorders and dementia.
Patients not extubated on the table and reintubated within the duration of study period. 
 
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 report the incidence of delirium between melatonin and placebo group.  post operative day 1 till post operative day 5 
 
Secondary Outcome  
Outcome  TimePoints 
Duration of delirium.
Severity of delirium.
Length of hospital stay.
Total dose of haloperidol and benzodiazepines administered during delirium.
In hospital mortality rate.
ICU admittance and length of stay 		 5 days or 120 hours 
 
Target Sample Size   Total Sample Size="100"
Sample Size from India="100" 
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)   31/07/2024 
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)
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  

 Post-operative delirium (POD), as a phenotype of delirium, occurs in approximately 10-50% of patients after major surgery. Post-operative delirium is a common, serious, under-recognized adverse event and is associated with significant morbidity and mortality in elderly patients. While delirium may occur in every patient after surgery, the incidence is higher in the elderly patient. Post- operative delirium in the elderly occurs in 10% to 61% of those aged 65 or older.ost-operative delirium and the associated risk factors have been studied quite extensively in patients having orthopaedic or cardiac surgery and recent studies report incidence of delirium of up to 24% in patients with critical limb ischemia. The identified risk factors of postoperative delirium in lower limb ischemia are age, end-stage renal failure, multiple occlusive lesions, cognitive impairment, and critical limb ischemia. Critical limb ischemia (CLI) is the term used to delineate the condition in which arterial disease has resulted in pain in the foot even at rest or in a breakdown of the skin (ulcer or gangrene), and it is the most advanced form among peripheral artery disease. Despite such high incidence, the treatment and prevention of POD remain elusive in these sub-group patients. 

Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced in the brain by the pineal gland from the amino acid tryptophan. Synthetic melatonin supplements have been used for various medical conditions, most notably sleep-related disorders. It has been used successfully  when  used  as  a  premedication  to  decrease  anxiety  and  sedate  patients preoperatively with an excellent cognitive profile. Moreover, it has been found that melatonin levels drop after the surgery. Sleep disturbances result in serious physiological consequences such as delirium, which may negatively influence the patients outcomes. The use of melatonin to prevent delirium in clinical studies is promising, and the reported decrease in delirium incidence in elderly patients hospitalized in medical wards was up to 50%. Concerning the perioperative period, only a few small studies with conflicting results are available, and there is a paucity of literature and data to support or refute its role in vascular surgery patients specifically in patients undergoing reperfusion surgery for chronic limb ischaemia. Given the inconsistencies in the previous studies concerning the prevention of post operative delirium, as well as the limited studies in this area and to test the hypothesis that short-term administration of oral melatonin will reduce the incidence of postoperative delirium in patients undergoing elective reperfusion surgeries, this placebo controlled, double blind, randomized clinical trial will be carried out. The research question for this study is to determine the effect of melatonin on prevention of postoperative delirium in patients aged 40 -75 years of age undergoing reperfusion surgery for chronic lower limb ischemia.

All patients who will be undergoing bypass surgery for chronic limb ischemia will be approached within 24 hours of admission by the researcher. Patients will be screened for eligibility, and proper consent will be taken. After randomization, the patient will receive the study medication on two consecutive evenings, on the evening before surgery and one day prior to the day before surgery (at seven p.m.).

At baseline, we will record demographic data, medical history, medication use, and surgery related characteristics. We will also observe intraoperatively for any general and specific complications, drugs used for anaesthesia, any infusion applied, and lab and hemodynamic data. All patients enrolled in the study will be screened at least once daily using the 4AT assessment method administered by the investigator. The development of delirium will be observed from post-op day 1 to post-op day 5. We will not protocolize the administration of any co-interventions in this study. Pain, agitation, sedation, delirium, and sleep management will be performed according to institutional practice.

References-

1. Sultan SS. Assessment of role of perioperative melatonin in prevention and treatment of post-operative delirium after hip arthroplasty under spinal anesthesia in the elderly. Saudi J Anaesth 2010; 4: 169-173. DOI: 10.4103/1658-354x.71132.

2. Wang CM and Zhou LY. Melatonin and melatonergic agents for the prevention of post- operative delirium: A meta-analysis of randomized placebo-controlled trials. Asian J Surg 2022; 45: 27-32. 20210604. DOI: 10.1016/j.asjsur.2021.04.041.

3. Raats JW, Steunenberg SL, de Lange DC, et al. Risk factors of post-operative delirium after elective vascular surgery in the elderly: A systematic review. Int J Surg 2016; 35: 1-6. 20160906. DOI: 10.1016/j.ijsu.2016.09.001.

4. You W, Fan XY, Lei C, et al. Melatonin intervention to prevent delirium in hospitalized patients: A meta-analysis. World J Clin Cases 2022; 10: 3773-3786. DOI: 10.12998/wjcc.v10.i12.3773.

5. Burry L, Scales D, Williamson D, et al. Feasibility of melatonin for prevention of delirium in critically ill patients: a protocol for a multicentre, randomised, placebo- controlled study. BMJ Open 2017; 7: e015420. 20170330. DOI: 10.1136/bmjopen-2016- 015420.

6. Sigaut S, Couffignal C, Esposito-Farèse M, et al. Melatonin for prevention of post- operative delirium after lower limb fracture surgery in elderly patients (DELIRLESS): study protocol for a multicentre randomised controlled trial. BMJ Open 2021; 11: e053908. 20211224. DOI: 10.1136/bmjopen-2021-053908.

7. Vasilevskis EE, Han JH, Hughes CG, et al. Epidemiology and risk factors for delirium across hospital settings. Best Pract Res Clin Anaesthesiol 2012; 26: 277-287. DOI: 10.1016/j.bpa.2012.07.003.

8. Böhner H, Hummel TC, Habel U, et al. Predicting delirium after vascular surgery: a model based on pre- and intraoperative data. Ann Surg 2003; 238: 149-156. DOI: 10.1097/01.sla.0000077920.38307.5f.

9. Steiner LA. Post-operative delirium. Part 1: pathophysiology and risk factors. Eur J Anaesthesiol 2011; 28: 628-636. DOI: 10.1097/EJA.0b013e328349b7f5.

 
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