RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BENGALURU, KARNATAKA

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1 / Name of the candidate and address (in block letters) / DR.Kavya K.S
POST GRADUATE STUDENT(MD)
DEPARTMENT OF ANAESTHESIOLOGY, VYDEHI INSTITUTE OF MEDICAL SCIENCES & RESEARCH CENTRE, WHITEFIELD, BANGALORE.
2 / Name of the Institution / VYDEHI INSTITUTE OF MEDICAL SCIENCES AND RESEARCH CENTRE
BANGALORE - 560 066
3 / Course of the study and subject / M.D. ANAESTHESIOLOGY ( 3 years )
4 / Date of admission to course / 06-06-2013
5 / Title of the topic
TRANS-DERMAL FENTANYL PATCHES IN COMPARISON TO ORAL SUSTAINED RELEASE MORPHINE TABLETS TO RELIEVE CHRONIC PAIN IN PATIENTS WITH ADVANCED CANCER
6 / BRIEF RESUME OF THE INTENDED WORK
6.1  Need for the study
Inspite of advanced therapy for cancer many do not get cured and the process of malignancy continues resulting in pain and suffering. Although cancer pain or associated symptoms often cannot be entirely eliminated, appropriate use of available therapies can effectively relieve pain in most patients. The main objective of palliative care is to improve the quality of life and relieve the patient from pain and suffering. Opioids are the mainstay of management of cancer pain, providing effective pain relief.
1Morphine is an opioid and the usually prescribed starting dose is 5-10mgs administered at 4 hourly intervals. Many Hospice centres give double dose at bedtime to avoid waking-up from sleep. Once pain relief is optimal and stable patient can be switched over to sustained release preparations to allow 12 hourly dosing. Morphine is more commonly associated with sedation, nausea ,vomiting,dry mouth andsevere constipation.
Fentanyl is a synthetic opioid agonist which interacts primarily with the mu-opioid receptor. 7The low molecular weight, high potency and lipid solubility of fentanyl makes it suitable for delivery by the transdermal patches providing continuous, controlled systemic delivery of fentanyl These patches are designed to deliver fentanyl at a constant rate (25, 50, 75 and 100 microg/h), and require replacement only once in 3 days.
Studies with transdermal fentanyl have shown analgesic efficacy in cancer pain.Most patients prefer fentanyl, which is associated with less constipation, no oral dosing and lesser associated complications than oral morphine and hence the present study has been undertaken
6.2  Objectives of the study
1.  To compare the efficacy of Sustained release oral morphine and Transdermal fentanyl in respect to analgesia, adverse effects, dosing and quality of life
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2.  To assess the patient acceptability to the drugs.
6.3  Review of Literature
1Clark AJ et al …Trials with treatment durations of 28 days was conducted in patients with advanced cancer pain
- Assessed changes in averagepainandpain'right now' scores between baseline and Day 28
- Evaluated incidence of adverse events reported within the first 28 days of treatment with Trans-dermal Fentanyl or Sustained Release Morphine
•  Study concluded significant improvement in painrelief with transdermal fentanyl compared withsustained-releaseoralmorphine
•  Supports current evidence of favourable tolerability of transdermal fentanyl, particularly with regard to reduced constipation and somnolence.
5Muijsers RB et al .. An updated review of pharmacological properties and therapeutic efficacy of transdermal fentanyl patches in chronic cancer pain control concluded: -
•  Transdermal fentanyl is a useful opioid-agonist for the treatment of moderate to severe chronic cancer pain
•  - Advantages of transdermal fentanyl includes ease of administration and the 3-day application interval
-These factors coupled with a lower incidence of constipation are likely to contribute to the reported patient preference of transdermal fentanyl over sustained-release oral morphine.
2 Heiskanen T et al.. In a study of 202 cancer patients who required strong opioids for pain relief, significantly more patients preferred trans-dermal fentanyl to sustained-release oral morphine
•  This preference may have been related to the fact that transdermal fentanyl was associated with less constipation , less daytime drowsiness
1 Chinese Journal Of Cancer Research In another study of 474 patients with moderate to severe cancer pain treated with trans-dermal fentanyl matrix patch (TDF) up to 2 weeks
•  - All the patients were asked to record pain intensity, side effects, quality of life (QOL), adherence and satisfaction
-The initial dose of fentanyl was 25 μg/hr. titrated with opioid
- Trans-dermal fentanyl was changed every three days
•  Study showed that the new TDF is effective and safe in treating patients with moderate to severe cancer pain, and can significantly improve the quality of life.
7 / MATERIALS AND METHODS
7.1 Source of data
Patients with advanced malignancies admitted in the oncology department at Vydehi Institute of Medical Sciences which has a pain and palliative care clinic
The Bangalore Hospice trust (Karunashraya) located near vydehi institute of medical sciences is a hospice where patients with advanced malignancy are cared for during their last phase of life
7.2  Method of collection of data (including sampling procedure if any)
Randomized controlled study will be conducted on 60 patients after written informed consent. Initially all 60 patients will be given 10 mg of oral morphine every 4 hourly till the patient is relieved with pain and is stable. The amount of drug required is calculated. The patients will be later divided into two groups of which 30 patients are on the required amounts of Sustained release oral morphine and 30 patients are on required amount of transdermal fentanyl. The Analgesic doses of fentanyl equivalent to the patients' previous opioid dose will be calculated .Patients will be treated with fentanyl patches releasing 25, 50, 75 fentanyl/hr and sustained release oral morphine as 10, 30, 60 or 100mgtablets.
The study will be conducted for a period of 15 days.The primary efficacy variable is the patient's preference for transdermal fentanyl or sustained release oral morphine and their main reason for preference which is effective analgesia..Each day patients will be assessed for pain control compared with the previous day. Quality of life and pain intensity by visual analog scale (0 being low and 100 being max) will be assessed at baseline and everyday morning and evening. Details of all adverse events and presumed relation to the drugs will be noted .At each visit bowel function will be assessed by using a questionnaire.
INCLUSION CRITERIA:
1. Age – 20 to 65 years, of both sexes.
2. Advanced cancer patients with failed modalities of treatment willing to give a informed written consent
EXCLUSION CRITERIA:
1. Patients undergoing active treatment for malignancies
2. Patients with h/o allergy or hypersensitivity to opiods
3. Patients with skin diseases precluding the application of transdermal patches
Statistical methods applied:
ANOVA TEST
7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animal? If so, please describe briefly.
No
7.4 Has ethical clearance been obtained from your institution in case of
Yes
8 / ReferencesXin Ding,Bin Wang,Wei-lian Li,Zuo-wei Hu,Gang Feng,Jiang-jin Huang,Xiao Zheng,Shun-chang Jiao,Rong Wu,Jun Ren
1.  Multicenter clinical study for evaluation of efficacy and safety of transdermal fentanyl matrix patch in treatment of moderate to severe cancer pain in 474 Chinese cancer patients” Chinese Journal Of Cancer Research,December 2011, Volume 2,Issue 4,pp 317-322.
2.  Heiskanen T, Mätzke S, Haakana S, et al. International Association for the Study “Transdermal fentanyl in cachectic cancer patientsof Pain 2009” 218 -222.
3.  Clark AJ,Ahmedzai SH,Allan LG,Camacho F,Horbay GL,Richarz U,Simpson K. “ Efficacy and safety of transdermal fentanyl and sustained-release oral morphine in patients with cancer and chronic non-cancer pain” 2004 Sep;20(9):1419-28.

4.  GW Hanks1, F de Conno2, N Cherny3, M Hanna4, E Kalso5, HJ McQuay6, S Mercadante7, J Meynadier8, P Poulain9,C Ripamonti2, L Radbruch10, J Roca i Casas11, J Sawe12 RG Twycross13 and V Ventafridda1. “Morphine and alternative opioids in cancer pain the EAPC recommendations”British Journal of Cancer (2001) 84(5), 587–593 .

5.  Muijsers RB,Wagstaff AJ “Transdermal fentanyl: an updated review of its pharmacological properties and therapeutic efficacy in chronic cancer pain control” NCBI 2001;61(15):2289-307Xin Ding,

6.  Pål Klepstad, MD, Petter C. Borchgrevink, MD, PhD, and Stein Kaasa, MD, Phd “Effects on Cancer Patients’ Health-RelatedQuality of Life After the Start ofMorphine Therapy” Journal of Pain and Symptom Management .Vol. 20 No. 1 July 2000.

7. 

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7.  William Breitbart, MD1, Sonja Chandler, PharmD2, Barry Eagel, MD, Neil Ellison, MD4, Robert E. Enck, MD5, Mathew Lefkowitz, MD6, Richard Payne,MD7 “An Alternative Algorithm for Dosing Transdermal Fentanyl for Cancer-Related Pain ’’Cancer network,May 1, 2000 ONCOLOGY.Vol. 14No. 5Xiao Zheng,

1.  Shun-chang Jiao,
2.  Rong Wu,
3.  Jun Ren
4.  hide
9 / Signature of the candidate
10 / Remarks of the guide / Advanced stage cancer patients with no chances for remission of the disease require pain and palliative care.
Morphine has been the mainstay for pain relief.But has associated adverse reaction. Fentanyl-C has been preferred to be a more powerful analgesic with fewer side effects.
Efficacy of FTD patches has been compared in this study
11 / 11.1 Name and Designationof the Guide.
11.2 Signature / DR. SADANAND GOPAL M.D.
PROFESSOR
DEPARTMENT OF ANAESTHESIOLOGY,
VYDEHI INSTITUTE OF MEDICAL
SCIENCES AND RESEARCH CENTRE,WHITEFIELD,
BANGALORE.
11.3 Co-guide
11.4 Signature
11.5 Head of the Department
11.6 Signature / DR. SADANAND GOPAL M.D.
PROFESSOR
DEPARTMENT OF ANAESTHESIOLOGY,
VYDEHI INSTITUTE OF MEDICAL
SCIENCES AND RESEARCH CENTRE,WHITEFIELD,
BANGALORE.
12 / 12.1 Remarks of the Chairman and Principal
12.2 Signature