FULL DETAILS (Read-only)  -> Click Here to Create PDF for Current Dataset of Trial
CTRI Number  CTRI/2025/03/082707 [Registered on: 19/03/2025] Trial Registered Prospectively
Last Modified On: 19/01/2025
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 the enhanced effect of the combination of low-dose Methadone with Morphine in pain management for Gastrointestinal cancer patients when compared to Morphine alone for pain management in Gastrointestinal cancers 
Scientific Title of Study   Evaluating the efficacy of combination of low dose Methadone with Morphine vs Morphine for pain management in Gastrointestinal cancers- a Randomised Control 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  Dr Ajay Ram 
Designation  Junior Resident (MD), Palliative Medicine 
Affiliation  All India Institute of Medical Sciences, New Delhi  
Address  Palliative care unit, Room no-154, Dr BRA IRCH, All India Institute of Medical Sciences, Sri Aurobindo Marg, East Ansari Nagar, New Delhi- 110029

New Delhi
DELHI
110029
India 
Phone  8778927594  
Fax    
Email  ajayaakash16@gmail.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Sachidanand Jee Bharati 
Designation  Professor 
Affiliation  All India Institute of Medical Sciences, New Delhi  
Address  Room no- 139, First Floor, Dr BRA IRCH, All India Institute of Medical Sciences, Sri Aurobindo Marg, East Ansari Nagar, New Delhi- 110029

New Delhi
DELHI
110029
India 
Phone  9968436042  
Fax    
Email  sacidadr@yahoo.co.in  
 
Details of Contact Person
Public Query  
Name  Dr Sachidanand Jee Bharati 
Designation  Professor 
Affiliation  All India Institute of Medical Sciences, New Delhi  
Address  Room no- 139, First Floor, Dr BRA IRCH, All India Institute of Medical Sciences, Sri Aurobindo Marg, East Ansari Nagar, New Delhi- 110029

New Delhi
DELHI
110029
India 
Phone  9968436042  
Fax    
Email  sacidadr@yahoo.co.in  
 
Source of Monetary or Material Support  
Department of Oncoanaesthesia and Palliative Medicine, Dr BRA IRCH, All India Institute of Medical Sciences, New Delhi 
 
Primary Sponsor  
Name  Dr BRA IRCH , All India institute of Medical Sciences, New Delhi  
Address  Dr BRA IRCH , All India institute of Medical Sciences, Sri Aurobindo Marg, East Ansari Nagar. New Delhi - 110029 
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 2  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Ajay Ram  Dr. B.R.A Institute - Rotary Cancer Hospital  Room no:154 ,Palliative Care Unit,1st floor, Dr. B.R.A Institute - Rotary Cancer Hospital , All India Institute of Medical Sciences, East Ansari Nagar, Ansari Nagar, New Delhi - 110029
New Delhi
DELHI 		 8778927594

ajayaakash16@gmail.com 
Dr Ajay Ram  National Cancer Institute  Palliative Medicine Ward,1st floor, D wing ,Hospital block, National Cancer Institute-AIIMS, Badsa, Jhajjar, Haryana - 124105
Jhajjar
HARYANA 		 8778927594

ajayaakash16@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institute Ethics Committee For Post Graduate Research, AIIMS, New Delhi   Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C15-C26||Malignant neoplasms of digestive organs,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Evaluation of efficacy of combination of low dose oral Methadone syrup with Morphine tablets for pain in patients of Gastrointestinal cancers.  Analgesic optimization with the combination of low dose oral Methadone syrup (2.5 mg/ 0.5ml) with oral Morphine tablets for relief of pain in Gastrointestinal cancers and followed up for 1 month 
Comparator Agent  Evaluation of efficacy of oral Morphine tablets for pain in patients of Gastrointestinal cancers  Analgesic optimization with oral Morphine tablets for relief of pain in Gastrointestinal cancers and followed up for 1 month 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  Patients aged between 18 and 65 years
Patients with the diagnosis of Gastrointestinal cancers with abdominal pain on opioids
Patients for whom the pain is not adequately managed which is NRS less than 4 with 60 mg of Morphine per day are recruited into the study
Patient with the ability to provide informed consent and is willing to comply with study procedure and follow up visits and recruited into the study
Patients belonging to ECOG physical status classification I II and III are recruited into the study 
 
ExclusionCriteria 
Details  1. Patients with contraindications to Methadone like (Hypersensitivity, Acute or Severe bronchial asthma,
Paralytic ileus, Uncontrolled mental illness, Pregnancy, Severe Hepatic impairment, History of
conduction heart disorders, significant arrhythmias, heart block).
2. Inability to provide informed consent or comply with study procedures.
3. Patient taking other opioids like Fentanyl.
4. Patients who are on drugs which causes QTc prolongation (Antimalarials, Moxifloxacin,
Antidepressants, Antipsychotics , Antiarrhythmics, Fluconazole Etc.,)
5. Patients who are on drugs affecting cytochrome metabolism ( Protease inhibitors , Rifampicin ,
Ketoconazole etc.,)
6. Patients with significant dyselectrolytemia.
7. Old and frail patients, terminally ill patients who have less probability of being alive till the end of the
study duration. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
GI cancer pain is measured Numerical Rating Scale and compared between 2 groups.  Upon OPD visits at Presentation, 1st week, 2nd week, and 4th week. 
 
Secondary Outcome  
Outcome  TimePoints 
To evaluate the side effect profile of combination of low dose Methadone with Morphine and Morphine alone for pain management in Gastrointestinal cancers.   Patients will be evaluated at 1 week, 2 week and 1 month. 
To evaluate whether the addition of Low dose methadone with Morphine decreases the total opioid consumption.  Patients will be evaluated at 1 week, 2 week and 1 month. 
 
Target Sample Size   Total Sample Size="74"
Sample Size from India="74" 
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)   01/06/2025 
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 Yet Recruiting 
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  
According to GLOBOCAN 2022, approximately a quarter (24.6%) of all cancer cases worldwide are GI tract cancers, yet they account for more than one-third (34.2%) of all cancer-related deaths. Notably, the burden of GI tract cancers is disproportionately higher in Asia, where an estimated 63% of cases and 65% of deaths occur. Pain is a prevalent and distressing symptom experienced by many patients with Gastrointestinal cancer. It encompasses not only physical sensations but also emotional and psychological components, significantly impacting patient’s quality of life. Chronic cancer pain associated with GI cancers, often presents as a prolonged and fluctuating condition with ill-defined onset. The management of cancer related pain usually involves the combination of multiple drugs, with opioids as the key component of most therapeutic strategies. In some cases, pain is not relieved due to lack of efficacy of opioids or due to intolerable adverse reactions leading to refractory pain. Due to these reasons, Opioid rotation is frequently employed to improve pain relief while simultaneously avoiding opioid side effects. Methadone is usually used in opioid rotation due to its distinctive properties, including a rapid onset of action, prolonged action, high oral bioavailability, and incomplete cross-tolerance with other opioids. These characteristics make it an optimal choice for opioid rotation.
Morphine related side effects are one of the main reasons for starting opioid combination, as it can be a way to improve analgesic effect with less side effects. Methadone is a potent opioid that has usually been used in combination with other opioids. In a retrospective observational study, the authors concluded that “low doses of methadone could be associated with other opioids and could be part of first line treatment for palliative pain treatment”. In another retrospective case series study, the combination of methadone with other opioids provided better control of cancer-related pain. Another retrospective study conducted on patients who received methadone as a co analgesic opioid showed a reduction in pain intensity of >30% in about half of patients with cancer pain under palliative care. A national Swedish survey in specialized Palliative care upon conducting a survey came to a conclusion that the addition of low-dose methadone as a co analgesic to other ongoing opioid therapy appears to be a safe way to benefit from the unique pharmacodynamics of methadone, especially in patients with complex cancer-related pain at the end of life.
Another multicentre prospective study supports the validity of using methadone as an adjunct to opioid-based treatment for cancer pain, especially for patients already on high doses of opioids without adequate pain control. A RCT was done in Brazil to check the efficacy and feasibility of combination of morphine and low dose methadone for cancer pain management, which gave us a result that a combination of low dose methadone with morphine provided significantly less pain after 2 weeks of treatment and provides a good alternative for patients with cancer related pain that is difficult to control. Although this study was not planned to show differences in adverse effects no differences were noticed. Based on these previous literatures, and low usage and fear around using methadone as an analgesic, I wanted to design a study and plan a Randomized control trials to compare the efficacy of combination of low dose methadone with Morphine vs Morphine for cancer pain management in Gastrointestinal cancers.
 
Close