PG DEGREE (Batch 2020-21) SYNOPSIS FORMAT

PART A – GENERAL INFORMATION

1 Title of the Dissertation EFFICACY OF TOPICAL

PHENYTOIN VS

METRONIDAZOLE IN

DIABETIC ULCERS

2 A. Name of the Candidate with mobile number and email ID: Dr. CHIRAG.P.GOWDA

9448815909

chiragprakashgowda@gmail.com

3 B. Name of the Institute: SDM INSTITUTE OF

MEDICAL SCIENCES AND

RESEARCH

4 C. University Registration Number: 20MPG055

5 D. Name of the programme studying: MS, GENERAL SURGERY

6 E. University Program Code:

7 F. Year of Admission: 2020

8 G. Month and year of appearing for final examination 2023

9 H. Month and year of submitting Dissertation 2023

10 I. Name (s), Designation (s) & Addresses of the guide and

co-guide (s) with mobile numbers and email ID

Dr. SRINIVAS.B.PAI

HOD DEPARTMENT OF

GENERAL SURGERY,

SDM MEDICAL COLLEGE

9845547717.

11 A. State whether the study is intradepartmental or

interdepartmental:

INTERDEPARTMENTAL

ii. Mention whether consent has been obtained from

them (Copy to be Attached)

12 Total funds required for the study (in rupees):

13 Source of funding

PART B – TECHNICAL DETAILS

1 Title of the dissertation EFFICACY OF TOPICAL

PHENYTOIN VS METRONIDAZOLE

IN DIABETIC ULCERS

2 Introduction

A. Problem statement India is gradually moving ahead in

terms of largest number of diabetic

patients and is being predicted to be the

“World’s Diabetes Capital” by the year

2025.

According to data published by the

International Diabetes Federation, the

number of people with diabetes in India

is expected to rise to 142.7 million by

2035 unless urgent preventive steps are

taken. The ulcers of the foot are seen in

about 25% of diabetes patients. More

than 50% of the patients with foot

ulcers become infected, who require

hospitalization, out of these 20% of

infected wounds end up with

amputation.

B. Rationale Of all the non-traumatic

amputations performed in the Diabetic

patients make up about 80%. Those

patients with diabetic foot ulcer have a

40% greater 10-year death rate than

people with diabetes alone. Of the total

lower limb amputations, 85% are due to

Diabetic Foot Ulcers

The process of wound dressings have

been in practice for at least two

millennia, Surgical dressing of both

open and closed wound is based.

During the last two decades a wide

variety of innovative dressings have

been introduced. In any chronic wound

the healing process is slow, especially

in case of pressure ulcers and bed sores.

The wounds develop granulation tissue

much faster when proper moist dressing

is applied which leads to wound

healing.

The problem of chronic wound healing

is still prevalent, in spite of availability

of many modalities of wound care. As

the diabetic foot ulcer is so prevalent

the rationale of the study to know

which type of dressing provides better

treatment.

C. Novelty Phenytoin is a well-known medicine for

seizures it has been reported to have a

positive therapeutic impact on diabetic

foot ulcers in recent years through

external application because of

the enhancement of fibroblast

proliferation, collagen production and

granulation tissue formation. Present

study explores if the Phenytoin dressing

provides better results than the

metronidazole dressings.

D. Expected outcome and application Comparison of the results of wound

healing by the phenytoin and

metronidazole in diabetic ulcers. The

investigators will know which type of

the dressing will give better results.

3 Research question(s) Efficacy of topical phenytoin or

metronidazole is better in diabetic

ulcers

4 Research hypothesis (es), if any PHENYTOIN MAY BE BETTER

THAN METRONIDAZOLE IN

IMPROVING THE HEALING

PROCESS.

5 Objectives of the Study:

A. Primary objective(s)

B. Secondary objective(s)

Aim is to compare the effect of topical

phenytoin and Metronidazole dressing

on the healing process in diabetic

ulcers.

1. To find which dressing can be

used in better management of

diabetic ulcers in terms of:

Number of days required for

healing.

Rate of granulations tissue

formation.

Rate of reduction in mean ulcer

surface area.

Quality of graft bed.

Skin graft take up.

Serial culture and sensitivity of

wound swabs to assess the

effect of topical phenytoin on

bacterial load.

6 1. Review of literature Phenytoin wound healing mechanisms

may include:

1. Stimulation of fibroblast

proliferation.

2. Enhancing the formation of

granulation tissue.

3. Decreasing collagenase activity,

inhibition of glucocorticoid activity.

4. Direct or indirect antibacterial

activity by affecting inflammatory

cells.

5. Phenytoin increases gene expression

of the platelet derived growth factor p

chain in macrophage and monocytes.

Phenytoin, a well-known medicine for

seizures, has been reported to have a

positive therapeutic impact on diabetic

foot ulcers in recent years through

external application because of

the enhancement of fibroblast

proliferation , collagen production and

granulation tissue formation.

In a study conducted by Dr. Sudhir S,

in 2019 observed that group for which

Phenytoin dressing was done

underwent SSG or secondary suturing

in or < 2 weeks , whereas the other

group took more than 3 weeks.

In another prospective study

conducted by Sanjay Prasad, in the

year 2017, comprising of 50 patients

which were divided into two groups. In

group I patient’s conventional betadine

dressing was applied. In group II

patient’s phenytoin was used for the

dressing. Both the groups were

compared on various parameters like

time required for healing,

complications, grafting and the results

were statically evaluated. Results

showed that Increased rate of

granulation tissue formation was seen

in topical phenytoin group when

compared to conventional group. Better

graft take up was seen in topical

phenytoin group when compared to

conventional group. On contrasting the

number of days required for healing,

effect on bacterial load and side effects

of topical phenytoin dressing with

conventional betadine dressing, the

former yielded better results in all

respects. The study concluded that

Topical phenytoin dressing is an

effective, inexpensive and widely

available therapeutic agent in wound

healing in chronic diabetic ulcers.

In another study conducted by

DrJayaraman, in the year 2016, 100

patients with diabetic foot ulcer

attending Thanjavur Government

Medical College Hospital were

randomized into two groups, first group

was assigned regular saline and

betadine dressing for the control group.

Second group had phenytoin powder

application for the dressing. Both study

and control group were compared in

terms of number of days required for

healing, rate of granulations tissue

formation. Rate of reduction in mean

ulcer surface area. Quality of graft bed.

Skin graft take up and serial culture and

sensitivity of wound swabs to assess the

effect of topical phenytoin on bacterial

load. The results showed that the rate of

granulation tissue formation was

assessed at the end of 2 weeks; 81 to

90% granulation was seen in study

group. In study group, 84% cases graft

take up was good and 70% in the

control group. Graft take up was 72.4%

and 58.43% respectively. Hospital stay

21 days in study group and 45 days in

control group. The authors concluded

that the rate of granulation tissue

formation, overall graft survival and

patient compliance was better in topical

phenytoin dressing group as compared

to conventional dressing group

In another study conducted by J Shaw,

conducted in 2011participants were

treated for a maximum of 16 weeks.

Sixty per cent of the diabetic foot ulcers

closed overall (18 in the phenytoin

group, 20 in the control group) with no

statistically significant differences in

complete healing or in diabetic foot

ulcer area over time between the two

groups. At 24-weeks follow-up, one

diabetic foot ulcer had recurred. There

were no differences in diabetic foot

ulcer closure rates or in diabetic foot

ulcer area over time between the two

groups.

In another study conducted by

MR Pai in 2001With phenytoin, there

was a marginal: increase in the

reduction of mean ulcer area and

acceleration of effect 3rd on 4th week.

With control: the number completing

the trial was larger: response to

treatment was better in grade II ulcers.

Metronidazole gel [Ornidazole (IP-10

mg and water soluble gel base quantity

sufficient)] has good anaerobic

coverage and helps in maintaining a

moist wound healing environment. By

weight, gels are mostly liquid, yet they

behave like solids due to a three-

dimensional cross-linked network

within the liquid. It is the crosslinking

within the fluid that gives a gel its

structure (hardness) and contributes to

its adhesion

Both by weight and volume, gels are

mostly fluid in composition and thus

exhibit densities similar to those of

their constituent liquids, such as

hydrogels. Topical metronidazole gel

(0.75%-0.80%) is frequently used

directly on the wound once per day for

five to seven days or more often as

needed.

and metronidazole tablets can be

crushed and placed onto the ulcer bed.

There are numerous other articles (case

studies or anecdotal experience)

reporting the reduction of wound odor

with topically applied metronidazole.

In another study by KhalilurRahman A

in 2018 , A total of 83 patients were

evaluated age ranged between 20 to 80

years with maximal clustering between

51-60 years of age. Poor glycemic

control and diabetes for more than 5 –

10 years increase the risk of foot ulcer.

Usage of Povidone Iodine, Eusol and

Metronidazole did not offer any healing

benefit when compared to normal

saline dressing.

7 2. Methodology

A. Study design RANDOMIZED CONTROLLED

PARALLEL-ARM DOUBLE

BLINDED STUDY

B. Study participants (human, animals or both) Humans

i. Inclusion criteria

ii. Exclusion criteria

iii. Withdrawal criteria, if any (trial-related

therapy, follow-up and documentation are

terminated prematurely as it is indicated to

ensure safety of the participants)

INCLUSION CRITERIA

Patients giving consent

Patients with age between 25 - 75 years

Patients with ulcers with diabetic

iv. Rescue criteria, if applicable (starting

symptomatic therapy either to control

symptoms of disease or to overcome lack of

adequate efficacy of the study drug or placebo)

v. Number of groups to be studied, identify

groups with definition

mellitus.

Wound size <5% TBSA

EXCLUSION CRITERIA

Chronic non-healing wounds of other

etiology.

Diabetes mellitus with gangrenous

changes.

Other co-morbid condition like renal

failure, generalized debility and other

factors, which adversely affect wound

healing

Non cooperative patient.

C. Sampling

a. Sampling population

b. Sample size calculation

c. Sampling technique

A total of 64 patients will

enter this 2 treatment parallel

designed study. The

probability is 60% that the

study will detect, a treatment

difference at 2 sided 0.05

significance lelev,

considering the effect size is

6.26 and so is 5.5.

Minimum of 64 cases

satisfying the inclusion and

exclusion criteria and are

presented in the time period

between 01/08/2020 to

01/08/2023 will be included

in the study.

D. Randomization details (for interventional

studies)- Intervention details with

standardization techniques (drugs / devices /

invasive procedures / noninvasive procedures /

others)

The whole sample population will be

divided into two equal and comparable

groups based on willingness for

undergoing therapy for wound. The

patients will be randomly assigned to

either of the two groups of either

metronidazole or phenytoin, the

patients will be blinded(double) and

they will not be aware of the group to

which they are allotted. Random

numbers for allotment will be taken by

the computer generated number.

E. Ethical Clearance from the Institution’s Ethics

Committee Obtained? (Copy to be Attached)

F. Study procedure The data will be collected from 100

patients with diabetic ulcers satisfying

all the inclusion criteria mentioned

above. The whole sample population

will be divided into two equal and

comparable groups based on

willingness for undergoing therapy for

wound. The patients will be randomly

assigned to either of the two groups of

either metronidazole or phenytoin, the

patients will be blinded and they will

not be aware of the group to which they

are allotted. Random numbers for

allotment will be taken by the computer

generated number. All patients will

undergo detailed clinical examination

and relevant investigations and the

wounds will be thoroughly debrided

and the ulcer dimensions as well as the

surface area assessed using Vernier

calipers, before both types of dressings

will be applied. The patients will be

followed up on a daily basis for 14 days

in both study and control groups. The

control group and study group will be

subjected to twice-daily dressing.

During the course of the treatment the

patient and the study variables will be

followed up in detail.

METHOD OF PREPERATION OF

DRESSING

PHENYTOIN

Dosage- 100% phenytoin, 10 mg/cm2.

Preparation- phenytoin tablet powder

mixed in NS(0.9%).

Frequency of application- once daily.

METRINIDAZOLE

Dosage- 100% metronidazole, 10

mg/cm2.

Preparation- metronidazole tablet

powder mixed in NS(0.9%).

Frequency of application- once daily

G. Data collection methods including settings and

periodicity

The patients will be followed up on a

daily basis for 14 days in both study

and control groups. The control group

and study group will be subjected to

twice-daily dressing. During the course

of the treatment the patient and the

study variables will be followed up in

detail.

H. List of statistical tests to be used for data

analysis

The variables in the study will be coded

and entered in MS excel 2016,

Continuous variables will be expressed

as Mean ± Standard Deviation and

compared across the groups using

paired t test or ANCOVA.

Categorical variables will be expressed

as number of patients and percentage of

patients and compared across the

groups. The statistical software SPSS

version 16 will be used for the analysis.

An alpha level of 5% will be taken, i.e.

if any p value is less than 0.05 it will be

considered as significant.

I. If it’s a Clinical Trial: Clinical Trials Registry of

India or equivalent registration number to be

mentioned

8 3. List risks and benefits of the study Risks

1. patient may have some kind of

reaction to the drug

Benefits

1. The patients will have effective

treatment and healing of the wound

9 4. Relevant references for the project

(Minimum 10, Maximum 20) (in Vancouver style)

1. Powers AC. Diabetes mellitus. In:

Longo D, Fauci A, Kasper D, Hauser S,

Jameson J, Loscalzo J, editors.

Harrison’s principles of internal

medicine. 18th ed. New York:

McGraw-Hill; 2012. p. 2968–3002..

2.Whiting DR, Guariguata L, Weil C,

Shaw J. IDF diabetes atlas: global

estimates of the prevalence of diabetes

for 2011 and 2030. Diabetes Res ClinPr

2013;94(3):311-21.

3. Pendsey S. Reducing diabetic foot

problems and limb amputation: An

Experience from India. In: Dinh T,

editor. Global Perspective on Diabetic

Foot Ulcerations. Croatia: InTech;

2011. p. 15-24.

4.Robert G.Frykberg, et al, The journal

of foot and ankle surgery , Diabetic

Foot Disorders , A clinical Practice

Guideline .Page 22-24 sep/oct- 2006

5. Lodha SC, Lohiya ML, Vyas MCR,

SudhaBhandari, Goyal RR, Harsh MK.

Role of phenytoin in healing large

abscess cavities. Br J Surg 1991;

78:105-8.

6. Muthukumarasamy MG, Sivakumar

G, Manoharan G. Topical phenytoin in

diabetic foot ulcers. Diabetes Care

1991; 14:909-11.

7. Rhodes RS, Heyneman CA,

Culbertson VL, Wilson SE, Phatak

HM. Topical phenytoin treatment of

stage II decubitus ulcers in the elderly.

Ann Pharmacother 2001; 35:675-81.

8. Modaghegh S, Salehian B, Tavassoli

M, et al. Use of phenytoin in healing of

war and non-war wounds. A pilot study

of 25 cases. Int J Dermatol 1989;

28:347-350.

9.Anstead GM, Hart LM, Sunahara JF,

Liter ME. Phenytoin in wound healing.

Ann Pharmacol 1996; 30:68-75.

10. Ta1as G, Brown RA, McGrouther

A. Role of phenytoin in wound healing-

a wound pharmacology perspective.

BiochemPharmacol

11. Genever PG, Cunliffe WJ, Wood

EJ. Influence of the extracellular matrix

on fibroblast responsiveness to

phenytoin using In vitro wound healing

models. Br J of Dermatol 1996;

133:231-35.

12.Sudhir S. To compare the efficacy of

topical phenytoin over conventional

wound care (5% povidone-iodine) in

diabetic ulcer. International Journal of

Surgery. 2020;4(1):122-8.

13. Prasad S, Prakash A, Patel S,

Lunawat A, Mahore D. A comparative

analysis of the efficacy of topical

phenytoin with conventional wound

dressing in healing of diabetic foot

ulcers. International Surgery Journal.

2017 Mar 25;4(4):1389-93.

14.Selvaraj J, Jeevaraman S. Efficiency

of topical phenytoin on healing in

diabetic ulcer: a randomized control

trial. Journal of Evolution of Medical

and Dental Sciences. 2016 Mar

21;5(23):1225-9.

15. Shaw J, Hughes CM, Lagan KM,

Bell PM. The clinical effect of topical

phenytoin on wound healing: a

systematic review. British Journal of

Dermatology. 2007 Nov;157(5):997-

1004.

16. Pai MR, Sitaraman N, Kotian MS.

Topical phenytoin in diabetic ulcers: a

double blind controlled trial. Indian

journal of medical sciences. 2001

Nov;55(11):593.

17. Kalinski C, Schnepf M, Laboy D,

Hernandez LM, Nusbaum J, McGrinder

B, Comfort C, Alvarez OM.

College af Medicul Sciences & IlospitulMmiushree Ncgcr, Saltur. Ilhnrwad - 58000$, I(nrnatrkc, INDIA

A Constitu ent U n it'of Shri Dharmasthala Mdnjunatheshwara UniversityRecognlbed by Medical Council of India, New Dethi

SHRIDHARMASTHALA

MANJUNATHESH RA

UNIVERSITY

Ref: SDMCMS&H/ IEC: 56 :2O2L Dare: !9-O2-202L

SUB: - Institutional Ethits Committee permission.

Permission is granted to the following postgraduate student to carry out the dissertation study :

Name of Postgraduate student: Dr. Chirag P Gowda

Title of the dissertation study: EFFICACY OF TOPICAL PHENYTOIN VS METRONIDAZOLE

IN DIABETIC ULCERS

Member Secretary-SDM I EC

I,S, S--'rrDr.Sujata Giriyan

Chairperson-SDMIEC

Dr. Sujata S. GlrtpnChairman

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