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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE,
KARNATAKA
ANNEXURE –II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1
NAME OF THE CANDIDATE
DR. CHANDRASHEKAR B M
AND ADDRESS
POST GRADUATE STUDENT
(IN BLOCK LETTERS)
DEPARTMENT
OF
RAJARAJESWARI
DENTAL
PERIODONTOLOGY
COLLEGE
AND
HOSPITAL, MYSORE ROAD,
BANGALORE – 560074.
2
NAME OF THE INSTITUTION
RAJARAJESWARI DENTAL COLLEGE
AND HOSPITAL, BANGALORE-560074.
3
COURSE
OF
STUDY
SUBJECT
4
AND MASTER OF DENTAL SURGERY
PERIODONTOLOGY
DATE OF ADMISSION TO THE 28.05.2013
COLLEGE
5
TITLE OF THE TOPIC: COMPARATIVE EVALUATION OF ANALGESIC EFFICACY
OF ORAL DICLOFENAC SODIUM AND TRANSDERMAL PATCH (NUPATCH®)
AFTER
PERIODONTAL
CLINICAL TRIAL
FLAP SURGERY: A RANDOMIZED CROSS OVER
6
BRIEF RESUME OF THE INTENDED WORK:
6.1 NEED FOR THE STUDY :
Successful periodontal treatment is not only based on correct surgical technique but also on the
prevention and management of postoperative pain and complications.
It was observed that 79% of patients complained of pain after open flap debridement, 89% after
gingivectomy, and 93% after flap surgery with osseous resection.1 Many factors may influence pain
intensity, such as the nature, duration, and extent of the surgery, and psychological aspects, such as stress
and anxiety. A common source of postoperative pain after periodontal surgery is extensive and excessively
prolonged exposure and dryness of bone.2
Non-steroidal anti-inflammatory drugs (NSAIDs) are most widely used to relieve oral postsurgical
pain. Diclofenac sodium is commonly prescribed NSAIDs, which has an anti-inflammatory and analgesic
property. Through oral route, only 50% of the absorbed dose of diclofenac becomes systemically available
due to first pass metabolism. Due to high plasma concentration, oral diclofenac carries significant adverse
reaction like gastric irritation, ulcers, and allergies.3
Recently, transdermal patches have been introduced to overcome the disadvantages of oral
analgesics. When it is applied to the unbroken skin, it delivers the contained drug at a constant rate into
systemic circulation via stratum corneum.4 The NuPatch® has potential advantage over oral diclofenac
because of its low systemic concentration there by reducing the risk of upper GI complications such as
gastric and peptic ulcers.
Therefore, the need for this study is to compare and evaluate the effect of transdermal patch
(NuPatch®) and oral diclofenac sodium (Divon®) on postoperative analgesia, adverse reactions like gastric
irritation, allergy, and patient tolerance and compliance following periodontal surgery.
6.2 REVIEW OF LITERATURE:

A study was done to compare the efficacy and time of analgesia of a new
tramadol/acetaminophen combination tablet to those of tramadol or acetaminophen (APAP) alone. The
1197 patients (age range, 16-46 years) were evenly randomized to a single dose of tramadol/APAP (75
mg/650mg), tramadol 75 mg, APAP 650 mg, ibuprofen 400 mg, or placebo. Active control with ibuprofen
was used to determine model sensitivity. Pain relief (scale, 0-4) and pain intensity (scale, 0-3) were reported
at 30 minutes after the dose and then hourly for 8 hours. Total pain relief over 8 hours (TOTPAR8) and the
sum of pain intensity differences (SPID8) were calculated from the hourly scores. Time to onset of pain
relief was determined by the double-stopwatch technique, and patients were advised to wait at least 2 hours
before taking supplemental analgesia. Pain relief provided by tramadol/ APAP was superior to that of
tramadol or APAP alone, as shown by mean TOT-PAR8 (12.1 vs 6.7 and 8.6, respectively, P < or = .0001)
and SPID8 (4.7 vs 0.9 and 2.7, respectively, P < or = .0001). Estimated onset of pain relief was 17 minutes
for tramadol/APAP compared with 51 minutes for tramadol, 18 minutes for APAP, and 34 minutes for
ibuprofen.5
 Another study was done to compare ketoprofen to acetaminophen with hydrocodone (A/H) in a
postoperative periodontal pain model. A double-blind protocol was used. Thirty minutes prior to each
procedure, subjects were given orally either 100 mg ketoprofen or a placebo tablet. Four hours later, the
subjects took either 50 mg ketoprofen (ketoprofen group) or 1000 mg acetaminophen with 10 mg
hydrocodone (placebo group). Subjects reported levels of overall discomfort and pain using visual analog
scales at eight hourly intervals following the first dose of ketoprofen or placebo. The results revealed only
small differences between the two drug regimens with respect to levels of pain or overall discomfort. A/H
provided significantly better pain relief at hours 5 and 6, while overall discomfort levels were significantly
higher with ketoprofen than with placebo at hours 3 and 4.6

In this study, the efficacy of a nonsteroidal anti-inflammatory agent, ketorolac tromethamine,
was evaluated for pain control after periodontal surgery. Two groups consisting of 40 patients who were to
undergo periodontal surgery were randomly given either 10 mg ketorolac immediately before surgery or
placebo tablets at least 30 minutes before administration of local anesthesia (LA). All procedures were
performed under LA. The duration of surgery from the time of incision to the placement of the last suture
was recorded. At the completion of the surgery, patients were asked to rate their subjective operative pain
intensity using a visual analog scale. The results showed that 10 mg ketorolac administered immediately
before periodontal surgery was effective for alleviating the operative painful sequelae.7

This study was done to evaluate the analgesic efficacy of diclofenac mouthwash after periodontal
surgery. In this double-blind, randomized clinical trial study 20 quadrants of 10 patients(n = 20) aged
between 22-54 who also acted as their own controls, were treated using Modified Widman Flap procedure
in two quadrants of the same jaw with one month interval between the operations. After the operation in
addition to ibuprofen 400 mg, one quadrant randomly received Diclofenac mouthwash (0.01%) for 30
seconds, 4 times a day (for a week) and for the contrary quadrant, ibuprofen and placebo mouthwash was
given to be used in the same manner. The patients scored the number of ibuprofen consumption and their
pain intensity based on VAS index in a questionnaire in days 1, 2, 3 and the first week after operation. The
findings were analyzed using two way ANOVA, t-test and Wilcoxon. There was a significant difference
between the mean values of pain intensity of two quadrants in four periods (P = 0.031). Postoperative
satisfaction was not significantly different in two quadrants (P = 0.059).8

This study was performed to compare the degree of post operative analgesia, patient compliance,
and frequency of adverse events with the use of oral diclofenac tablets and transdermal diclofenac patch
following multiple premolar extractions in patients undergoing orthodontic treatment. Twenty young preorthodontic patients requiring bilateral maxillary and mandibular first premolar extractions were selected
for the study. The right maxillary and mandibular first premolars were extracted first and 50 mg oral
diclofenac sodium tablets were prescribed to be taken thrice a day for three days. In the next appointment,
the contralateral first premolars were extracted and a 100 mg transdermal diclofenac patch was applied
once a day for three days. Pain relief and pain intensity with both the diclofenac formulations was recorded
for each of the three postoperative days using 5-point Verbal Pain Intensity and Pain Relief Score Charts.
Statistical analyses revealed that there were no significant differences in the pain relief and pain intensity
scores between transdermal patches and oral diclofenac sodium. Results of this study indicate that the
transdermal diclofenac patch provides potent analgesia as compared to the oral diclofenac tablets with the
added advantage of better patient compliance.3

Postoperative analgesic efficacy and associated side effects of a transdermal diclofenac patch
100 mg (NuPatch® 100) and intramuscular diclofenac sodium 75 mg (Voveran®) was evaluated in this
study. Sixty participants in the study were randomly allocated to two groups of 30 each, by a computergenerated randomization table. The anesthetic procedure was standardized. A transdermal diclofenac patch
100 mg was applied to the participants in the study group at the beginning of the lower limb orthopedic
surgery. In the control group, 75 mg of diclofenac sodium was given intramuscularly half an hour before
the end of surgery. Pain was assessed postoperatively at two-, six-, and 12-hour intervals using a visual
analogue scale (VAS). An injection of tramadol 2 mg/kg was administered intramuscularly as rescue
analgesia. The study ended when the patients asked for rescue analgesia, or when the VAS score was > 5.
The mean duration of analgesia in the control group was 7 hours 28 minutes, and in study group, it was 8
hours 6 minutes, which was comparable (p-value < 0.341). Results showed that intraoperative application
of a single dose of 100 mg transdermal diclofenac patch is as effective as a single dose of intramuscular
diclofenac (75 mg) for acute postoperative pain, without any significant side-effects.9
6.3 AIMS AND OBJECTIVES OF THE STUDY:
1) To compare and evaluate the analgesic efficacy of transdermal patch (NuPatch®) and oral
diclofenac sodium (Divon®) during postoperative period in patient undergoing quadrant periodontal
flap surgery.
2) To compare and evaluate the patient’s compliance, tolerance, and adverse reaction following the use
of NuPatch® and oral Divon®.
MATERIALS AND METHODS:
7.1 SOURCE OF DATA
7.1.1. Type of study: Randomized comparative cross over clinical trial.
7.1.2. Study population: Patients visiting the Department of Periodontology, Rajarajeswari Dental College
and Hospital, Bangalore.
7.2 METHOD OF COLLECTION OF DATA:
The patients in the age group of 25-50 years having chronic generalized periodontitis requiring
periodontal flap surgery in at least minimum of two quadrants will be recruited for the study. A total of 60
surgical quadrants will be divided into two groups as follows:
Group I (30 quadrants): Divon® 50 mg b.i.d will be given for three days in patients undergoing flap
surgery in one quadrant.
Group II (30 quadrants): NuPatch® 100 mg once daily will be given for three days to be applied on the
deltoid region after second quadrant flap surgery.
INCLUSION CRITERIA:
The patients diagnosed with chronic generalized periodontitis requiring resective or regenerative osseous
surgery in any of the two quadrants of their mouth will be included for the study.
EXCLUSION CRITERIA:

The patient with history of systemic diseases.

The patients who are undergoing treatment with analgesics or corticosteroids during the trial period.

The patients with history or clinical evidence of allergy to oral diclofenac or transdermal patch.

The patients who are suffering from peptic ulceration.

Pregnancy and lactating mothers.

Smokers and alcoholics.
SCREENING OF PATIENTS:
The quadrants which require resective or regenerative surgery will be confirmed through clinical
examination and radiography.
Pain Intensity and pain relief will be assessed postoperatively at two, six, and twelve hours on
the same day and also on the 2nd and 3rd day using pain scale chart consisting of Numerical Rating Scale ,
Visual Analog Scale, and McGills pain scale.
A proforma will be designed consisting of questionnaire regarding adverse reaction, patient
compliance, patient tolerance, and pain scale chart to have systematic and methodical recording of all the
observations and information. The relevant data will be recorded in the proforma.
METHOD OF SAMPLE COLLECTION:
All subjects will be explained the needs and objectives of the study. Only those subjects who
will agree to participate in the study will be included after obtaining a written informed consent. In each
patient, one quadrant will be randomly assigned to group I and group II. After successful completion of
phase I therapy, flap surgery will be performed. Local anesthesia using lidocaine 2% and epinephrine
1:100000 will be given prior to the surgical procedure. After performing periodontal flap surgery in one
quadrant, routine postoperative instructions will be given to the patients along with the advice to take
antibiotics and analgesics viz oral diclofenac tablets. Diclofenac sodium 50 mg will be given orally twice
daily for three days; and in the consecutive week, NuPatch® 100 mg will be applied to the hairless deltoid
region after completion of periodontal flap surgery on the other quadrant which will be followed for three
days on different areas. Postoperatively, the patients will be asked to report the intensity and pain relief on
the pain scale chart at two, six, and twelve hours and on 2nd and 3rd day which will be provided to them.
The patients will also be advised to record the number of diclofenac tablets or patches consumed and to
return the remaining tablets/patches to operator on their next visit. The patients will be recalled one week
postoperatively for suture removal and pain scale chart will be evaluated. The rescue medication tablets
taken, if any, would be noted and the patients will be asked if they experienced any adverse effects namely
gastric discomfort, nausea, vomiting, gastric acidity or burning sensation, dyspepsia, diarrhea, dizziness and
pruritus. The patient's satisfaction of the surgical technique will be assessed as well as their preference of
oral diclofenac or NuPatch®. The proforma will be collected and data will be statistically evaluated.
STATISTICAL ANALYSIS:

Descriptive statistics will be used to analyze demographic data.

Paired-t test will be used for analysis of data between the two groups.
DURATION OF STUDY: Nine months.
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTION TO BE
CONDUCTED ON PATIENTS OR OTHER HUMANS, ANIMALS? IF SO PLEASE DESCRIBE
BRIEFLY?
Yes. The study requires intervention as flap surgery will be performed in two quadrants under local
anesthesia; analgesics in the form of tablets and transdermal patches will be provided to the patient for pain
relief.
7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF
7.3?
Yes.
Ethical clearance letter has been attached.
8. LIST OF REFERENCES:
1. Steffens JP, Pochapski MT, Santos FA, Pilatti GL. Efficacy of anesthetic agents to delay pain onset
after periodontal surgery. Anesth Prog 2011;58(2):57–60.
2. Newman MG, Takei H, Klokkevold PR, Carranza FA. General Principles of Periodontal Surgery.
In: Carranza, editor. Carranza’s Clinical Periodontology. 10th Ed. Elsevier 2009:895.
3. Bhaskar H, Kapoor P, Ragini. Comparison of transdermal diclofenac patch with oral diclofenac as
an analgesic modality following multiple premolar extractions in orthodontic patients: A cross over
efficacy trial. Contemp Clin Dent 2010;1(3):158-163.
4. Tripathi KD. Routes of drug administration. In: Tripathi KD, editor. Essentials of Medical
Pharmacology. 6th Ed. Jaypee Brothers Medical Publishers (P) Limited;2009: 8-9.
5. Medve RA, Wang J, Karim R. Tramadol and acetaminophen tablets for dental pain. Anesth Prog
2001;48:79-81.
6. Reed KL, Smith JR, Lie T, Adams DF. A pilot study comparing Ketoprofen and Acetaminophen
with Hydrocodone for the relief of postoperative periodontal discomfort. Anesth Prog 1997;44:49-
54.
7. Hungund S, Thakkar R. Effect of pretreatment with ketorolac tromethamine on operative pain
during periodontal surgery: A case-control study. J Indian Soc Periodontal 2011;15(1):55-58.
8. Yaghini J, Moghareh A, Abed, Mostafavi SA, Roshanzamir N. The effect of diclofenac mouthwash
on periodontal postoperative pain. Dent Res J 2011;8(3):146-149.
9. Krishna R, Natraj MS. Efficacy of a single dose of a transdermal diclofenac patch as pre-emptive
postoperative analgesia: A comparison with intramuscular diclofenac. South Afr J Anaesth Analg
2012;18(4):194-197.