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ORIGIN L RTICLE

Effects of chlorhexidine/

benzydamine mouth spray on painand quality of iife in acute viraipiiaryngitis: A prospective,randomized, doubie-blind, piacebocontroiied, muiticenter study

Cemal C ingi, M D; Murat Songu, MD ; Ahm et U ral, MD; Muzeyyen Y ildirim, M D;Nagehan Erdogm us, MD ; Cengiz Bal, M D

Abstract

We eondueted a prospeetive, randomized, double-blind,

plaeebo-eontrolled, multieenterstudy to assess the effieaey

ofehlorhexidineglueonate/benzydamine HCl mouth spray

for redueingpain and improving quality of life in patients

with aeute viral pharyngitis. Prior to treatment, patients

rated the intensity of he ir pain on a visual analog seale and

evaluated their quality of life on the 36-Item Short-Form

Health Survey. Patients were then random ized to reeeive

either paraeetamol (aeetaminophen ) plus ehlorhexidine/

benzydam ine or paracetamo l plus plaeebo for 7 days. O n

days 3 and 7 of treatment, the partieipants again rated

the intensity of their pain, and on day 7 they again rated

their quality of life. A total ofl 64 patients were évaluable

at study s end— 80 in the ehlorhexidine/benzydam ine

group and 84 in the eontrol group. A eompa rison of

self-evaluations revealed that the aetive treatment g roup

reported less pain on both day 3 (p < 0.001 and day 7

(p = 0.002). Likewise, the ehlorhexidine/benzydam ine

group reported a signifieantly better quality of ife on day

(p < 0.001). ehlorhexidine/benzydamine was well toler-

ated, and no serious adverse events were observed.

From the Department of Otorhinolaryngology (Dr. Cingi and Dr. Er-

dogm us) and the De partm ent of Biostatistics (Dr. Bal), Osm angazi

University Medical Faculty, Eskisehir, Turkey; the Department of

Otorhinolaryngology, Dr. Behcet Uz Children's Hospital, Izmir,

Turkey (Dr. Songu); the Department of Otorhinolaryngology, Ka-

radeniz T echnical University Medical Faculty, Trabzon, Turkey (Dr.

Ural); and the De partm ent of Otorhinolaryngology, Dicle University

Medical Faculty, Diyarbakir, Turkey (Dr. Yildirim).

Corresponding au thor: Murat Songu, MD, Department of O torhinolar-

yngology, Dr. Behcet Uz Children's Hospital, 35210, Izmir, Turkey.

E-mail; [email protected]

Introduction

Acute pharyngitis is characterized by an inflamma- i

tion of the oropharyngeal cavity and the surrounding

lymphoid tissue.' Inflammation manifests as pain of

varying intensity. Viruses are the most common cause

of acute pharyngitis, being implicated in 40 to 60 of

cases.^'̂ Various reports put the incidence of bacterial

etiology between and 40 of cases.^' In cases of bacte-

rial infection, the most common pathogen is group A

beta-hemolytic Streptoeoeeus (GABHS).^'

Treatment of the cause of viral infections of the

oropharyngeal cavity is not possible, but symptom atic

treatment may reduce the intensity of pain to a great

extent. Numerous pharmaceutical agents that contain

disinfectants, anti-inflamm atory agents, and /or topical

anesthetics have been approved for the local treatmen t

of acute pharyng itis. However, to the best of our knowl-

edge, their effect on improving quality of life has not

been dem onstrated in double blind placebo-controlled

studies.^'''

We conduc ted a study to evaluate the effect of an in-

vestigational mouth spray that contains chlorhexidine

gluconate and benzydamine HCl in terms of reducing

the intensity of pain and improving quality of life in

patients with acute viral pharyngitis.

Patients and m ethods

Study design. The trial was designed as a prospee-

tive, randomized, double-blind, placebo-controlled,

parallel-group, muiticenter clinical study to test the

safety and efficacy of com bined chlorhexidine gluconate

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EFFECTS OF CHLORHEXIDINE/BENZYDAMINE MOUTH SPRAY ON PAIN AND OUALITY OF LIFE IN ACUTE VIRAL PHARYNGITIS:A PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY

and benzydamine HCl in relieving symptoms of acute

viral pharyngitis in patients who were also taking oral

paracetamol (acetam inophen). Between May 1 and Oct.

31, 2009, we recruited 188 patients at four hospitals

who had presented with complaints of sore throat and/or odynophagia. Because we wished to con centrate on

viral pharyngitis, we used the Centor criteria to exclude

patients with GABHS pharyngitis. Together, the Centor

criteria represent the most reliable clinical indicator of

GABHS pharyng itis. The four criteria are a history of

fever, the presence of tonsillar exudates, tend erness of

the anterior cervical lymph nodes, and an absence of

cough.̂ The positive predictive value of he C entor system

when all four criteria are met is 40 to 60 ; when only

one criterion is met the system has a negative predictive

value of 80 .' Compared with throat culture results,both the sensitivity and specificity of the Centor criteria

are 75 .' (Com plete inclusion and exclusion criteria are

listed in the table.)

Patients were random ized in a double-blind fashion

to one of two parallel treatment groups—paracetamol

plus chlorhexidine/benzydamine and paracetamol plus

placebo. The random ization was generated by the study

coordinator and senior author (CC). Numbered boxes

that contained either the active drug or placebo were

sent to clinical investigators at the four institutions. The

randomly generated n umber determined whether eachpatient received active drug or placebo. Details con-

cerning the contents of each box were unknown to the

investigators. The randomization code for each patient

was stored in two sealed envelopes. One set of envelopes

was kept by the study coordinator and the other set was

sent to the respective study center to be opened in case of

an emergency in the event that knowledge of the actual

treatment became medically necessary. Breaking the

code for one patient would no t automatically break the

code for the other patients. All investigators and patients

were blinded to treatment assignment through out thecourse of the study.

Self ratings. All patients self-rated the intensity of

their pain on a visual analogue scale (VAS) and their

quality of life on the 36-Item Short-Form SF-36) Health

Survey*'^ prior to treatment. The VAS ratings were made

again on the third day of treatment and on the last day

of treatment (7 days from baseline), while the repeat

SF-36 ratings were made only on day 7. The VAS was

graded on a scale of 0 (no pain) to 10 (the worst pain

imaginable).* For assessing quality of life, the SF-36 is a

well-documented, simple, standardized, and validatedsystem.*'̂ The range of SF-36 scores runs from 0 to 100,

Table. Inclusion and exclusion criteria

Inciusion

• Age >16 years

• History of sore throat S3 days• < Centor criterion

• Ability to understand and provide w ritten informed

consent and to report adverse events and concomitantmedication use for the duration of the study

Exclusion

• H istory of sore throat ^8 days

• Use of any medication, including herbs or dietary supple

ments, taken for relief of sore throat prior to study initiation• Current use of any analgesic or anti-inflammatory agents,

including steroidal and nonsteroidal drugs

• Symptoms of sore throat caused by local irritation of mu -

oous membranes as a result of gastroesophageal reflux• Pregnancy or a lack of contraception in women of childbearing potential

• Presence of a comorbid condition, uncontrolled metabolic

condition, or psychiatric co ndition that might make drugtolerance or evaluation difficult

with higher scores indicating a better quality of life.

reatmentThe scheduled treatment period was

7 days. Patients were allowed to continue treatment

beyond that point if symptoms persisted, but the extra

dosing was not factored into our results. Doses were

self-administered as a mouth spray 4 times per day.Paracetamol was taken at 500 mg 4 times daily. Patients

were instructed to avoid taking any other medication

for the relief of sore throa t. I

ide effects. Patients were asked to note any side ef-

fects of treatment on days 3 and 7 on a custom-designed

questionnaire. Local side effects th at have been repo rted

include taste disturbances, oral mucosal numbness,

burning sensation in the m outh, xerostomia or thirst,

and coloring of the teeth; systemic side effects include

nausea, vomiting, stomach ache, vertigo, and head ache .'

Patients evaluated the degree of side effects on a 4-point

Likert scale, with 0 points representing no side effects

and 1, 2, and 3 points denoting mild, moderate, and

severe side effects, respectively. Thus the possible scores

ranged from 0 to 30, with higher scores indicating worse

side effects.

t tistic l analysis. Data were analyzed with the Sta-

tistical Package for the Social Sciences software (version

17.0 for W indows; SPSS; Chicago). The Shapiro-WJilk

test was used to test the normality assumption. The

Student í test was used for paired samples, and repeated

measures were evaluated with the one-way analysis ofvariance (ANOVA). Values were expressed as means

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CINGI SONGU URAL YILDIRIM ERDOGMUS BAL

10

8 -

6 -

ic 4 -

2 -

Q Active drug

Placebo

Pretreatment Da y 3 Day 7

Figure 1. Chart shows the mean pre-, peri-, and post-treatment VAS scores for pain

intensity in the two groups. Subseque nt to the initiation of treatment the differences

between the two groups were statistically significant p < 0.001 on day 3 and p =

0.002 on day 7).

10 0 -

90 -

o 70 -

6 0 -

.? 50-

2 4 0 -

S 3 0 -

20 -

10 -

0 -

D Active drug

H Placebo

Pretreatment Day 7

Figure 2. Chart shows the mean pre- and post-treatment SF-36 scores for quality of life

in the two groups. The difference on day 7 was statistically significant p < 0.001).

(±SD ). Statistical significance was accep ted for p value s

of<0.05.

The study protocol was approved by the Ethics Co m-

mittee of Osma ngazi U niversity Med ical Faculty, and a

consent form was signed by each study patient.

Resuits

Of the 188 patients who met our inclusion criteria,

24 did not complete the trial. Five dropouts said they

could no t get time off work to attend the initiation and

follow-up sessions, ano ther 5 felt that treatm ent w as of

no benefit (3 in the active treatm ent gro up and 2 in the

control gro up), 3 said they were too ill to con tinue with

the trial, and 2 moved to a different area. The rest cited

various other reasons.

The final study pop ulation consisted of 164 patients—

94 males, aged 17 to 81 years (m ean: 37.43 ± 15.94) and

70 females, aged 17 to 71 years (mean: 38.31 ± 16.16).

Of these patients, 80 had been random ized to the active

treatmen t group and 84 to the control

grou p. The re were no significant dif-

ferences between the two groups in

the distribution of sex p = 0.413 and

ag e p = 0.935).All patients took their med ications as

directed, and no ne took any add itional

medication.

Intensity of pain Prior to treatm ent,

the m ean VAS score for pain intensity

was 7.41 ± 1.49) in the active tre atm en t

group and 7.76 (±1.51) in the control

group—not a statistically significant

difference p = 0.938). At day 3 of

treatment, the corresponding seores

were 4.15 (+1.20) and 6.31 (+1.06),whieh did represent a statist ieally

signifieant differenee p < 0.001). O n

day 7, the trend eontinued, as the re-

speetive seores were 2.83 (±1.09) a nd

5.01 (±0.99), whie h also represented a

signifieant differenee in favor of aetive

t reatment p = 0.002 (figure 1).

QuaíJíyo íi c At baseline, there was

no signifieant differenee in mea n SF-36

seores between the aetive treatment

group and the eontrol group—56.24(±18.44) and 48.50 (±16.80), respee-

tively p = 0.79). By day 7, however, th e

differenee betw een the two groups was

statistieally signifieant in favor of the

aetive treatment—71.34 (±11.10) and 54.37 (±12.10),

respeetively p < 0.001 (figure 2). In faet, a signifieant

improvement in quality of life over time oeeurred in

both the aetive treatment and eontrol groups p < 0.001 )

eompa red with baseline.

Side effects Analysis revealed no signifieant differenee

between the two groups in side effeet scores on either

day 3 (p = 0.403 or day 7 p ^ 0.938 (figure 3). The

degree of side effects was minor, and overall, the active

drug was well tolerated.

Discussion

Acute pharyngitis is one ofthe more com mo n co nditions

enco unte red in oflice practice, accoun ting for 2% of all

am bulato ry visits in the United States.^' Over t reatment

of acute pharyngitis represents one ofthe major causes

of antibiotic abuse, and the Centers for Disease Co ntrol

and Prevention have launched a campaign to dissuade

clinicians from routinely prescribing antibiotics for

8/12/2019 57418347


EFFECTS OF CHLORHEXIDINE/BENZYDAMINE MOUTH SPRAY ON PAIN AND OUALITY OF LIFE IN ACUTE VIRAL PHARYNGITIS-A PROSPECTIVE RANDOM IZED DOUB LE-BUND PLACEBO-CONTROLLED MULTICENTER STUDY

20 -,

16

A

I

12 -

8 -

4 -

pharyngitis. For patients with acute

pharyngitis, the goals of supportive

treatment are to reduce inñamm ation

and the intensity of pain while a ttempt-

ing to maintain oral intake in orderto avoid dehydration and subsequent

hospitalization.^ Such a strategy would

be expected to improve a patient's

quality of life.

At the moment, numerous phar-

maceutical products that contain dis-

infectants, anti-inflammatory agents,

and/or topical anesthetics are being

prescribed for the local treatment

of acute pharyngitis.^'^ In our study,

we used a mouth spray that containschlorhexidine and benzydam ine. Ghlorhexidine is an

antimicrobial agent that is frequently used for its topi-

cal antiseptie efïeets, and benzydamine is an effeetive

anti-inflammatory and analgésie. The effieaey of ehlo-

rhexidine against gingivitis and reeurren t uleers in the

oral mueosa has been d emonstrated in the literature.'^

Moreover, Bernstein et al eonfirmed the antiviral effi-

eaey of ehlorhexidine against influenza, parainfluenza,

eytom egalovirus, and herpes simplex virus infeetions.' *

Also, Park and Park showed the signifieant antiviral

effect of ehlorhexidine in vitro.

In our study, we found that ehlorhexidine/benzy-

dam ine mouth spray signifieantly redueed the intensity

of pain and signifieantly improved the quality of ife over

time. The eom bination exerted these benefieial effeets

without causing any serious side effects. Some pa tients

in the treatment group who did report side effects

cited some taste disturbances, oral mucosal numbness,

and discoloration of the teeth for a few days following

treatm ent. But overall, side effects w ere mild, and there

was no significant difference between the two groups

in side effect scores. This combination product was welltolerated at the prescribed dosage.

In conclusion, topical treatment modalities are

becoming more popular in view of their low rates of

systemic side effeets. We believe that ehlorhexidine/

benzydamine mo uth spray may prove to beeome a good

addition to the standard treatment arm amentarium for

aeute pharyngitis if our findings are borne out in further

researeh. We also believe tha t it would be worthwhile to

assess the effieaey of this treatment in GABHS tonsil-

lopharyngitis in larger sample sizes and with different

eontrol protoeols.

• Active drug

D Placebo

Day 3 Day 7

igure 3. Chart shows the mean Likert scale scores for side effects in the two groups.

Th e differences were not statistically significant on either day 3 (p = 0.403 or day

(p = 0.938 .

References1. Melio FR, Holmes DK. Up per respiratory tract infections. In: Rosen

P, Barkin RM, eds. Emergency Medicine. Concepts and ClinicalPractice. 4th ed. St. Louis: Mosby; 1998:1529-53.

2. Wei JL, Kasperbauer JL, Weaver AL, Boggust AJ. Efficacy of single-

dose dexametbasone as adjuvant tberapy for acute pharyngitis.Laryngoscope 2002; 112 1 ):87-93.

3. Shores CG. Infections and disorders of he neck and upper airway. In:Tintinalli JE, Kelen GD , Stapczynski JS, eds. Emergency Medicine.

A Comprebensive Study Guide. 6th ed. New York: McGraw-Hill;2004:1494-1501.

4. Coo per RJ, Hoffman JR, Bartlett JG, et al. Principles of appropriate

antibiotic use for acute pharyngitis in adults: Background. AnnIntern Med 2001;134(6):509-17.

5. Cento r RM, With erspoo n JM, Dalton HP, et al. The diagnosis ofstrep throat in adults in the emergency room. Med Decis Making

1981;l(3):239-46.

6. Diaz-B uxo JA, Lowrie EG, Lew NL, et al. Quality-of-life evaluation

using Short Form 36: Comparison in hemodialysis and peritonealdialysis patients. Am J Kidney Dis 2000;35(2):293-300.

7. McH orney CA, Ware JE Jr., Raczek AE. The MOS 36-Item Sh ort-Form Health Survey (SF-36): II. Psychom etric and clinical tests of

validity in measuring physical and mental health constructs. MedCare 1993;31(3):247-63.

8. Wewers ME, Lowe NK. A critical review of visual analogu e scales inthe measurement of clinical pbenom ena. Res Nurs Healtb 1990; 13

(4):227-36.

9. Field EA, Allan RB. Review article: Oral u lcération— aetiopatho-genesis, clinical diagnosis and mana geme nt in the gastrointestirialclinic. Aliment Pharmacol Tber 2003;18(10):949-62.

10. Snow V, Mottur-P ilson C, Cooper RJ, Hoffman JR; Am ericanAcademy of Family Pbysicians; American College of Physicians-American Society of Internal M edicine; Centers for Disease Control.Principles of appropriate antibiotic use for acute pharyngitis' in

adults. Ann Intern Med 2001;134(6):506-8. |

11. Matthijs S, Adriaens PA. Chlorh exidine varn ishes: A review. J ClinPeriodontol 2002;29(l):l-8.

12. Killoy WJ. Tbe use of ocally delivered cblorb exidine in the treatment

of period ontitis. Clinical results. J Clin P eriodontol 1998;25(11' Pt2):953-8; discussion 978-9.

13. BurgessJA,JohnsonBD,SommersE. Pharmacological managementof recurrent oral mucosal ulcération. Drugs 1990;39(l):54-65.1

14. Bern stein D, Schiff G, Echler G, et al. In vitro viru cidal effective-ness of a 0.12 -chlorhexidine gluconate mou thrinse. J Dent Res1990;69(3):874-6. |

15. Park JB, Park NH. Effect of chlorbex idine on tbe in vitro and in

vivo berpes simplex virus infection. Oral SurgO ral Med Oral Patbol1989;67(2):149-53.

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