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ORIGINAL RESEARCH—LARYNGOLOGY AND NEUROLARYNGOLOGY

Double-blind, placebo-controlled trial with

esomeprazole for symptoms and signs associated

with laryngopharyngeal reflux

Oliver Reichel, MD, Holger Dressel, MD, Katrin Wiederänders,

and

Wolfgang J. Issing, MD, PhD,

Munich, Germany; and Newcastle Upon Tyne, UK

OBJECTIVE:

To determine the efficacy of proton pump inhib-

itor (PPI) therapy with esomeprazole on symptoms and signs

associated with laryngopharyngeal reflux (LPR).

STUDY DESIGN AND METHODS:

Prospective, double-

blind, randomized, placebo-controlled study. Sixty-two patients

with a reflux finding score (RFS) 7 and a reflux symptom index

(RSI) 13 were enrolled and received either esomeprazole 20 mg

twice daily or placebo for three months. RSI and RFS were

assessed at baseline, after six weeks, and after three months.

RESULTS:

Reductions of total RSI and RFS as well as of

several subscores were significantly higher in the treatment group

compared to placebo after three months (

0.05 each). The

difference between study groups was most pronounced for poste-

rior commissure hypertrophy (

0.01).

CONCLUSION:

In the treatment of LPR-related symptoms a

high placebo effect can be observed. However, compared to con-

trol, twice-daily PPI treatment for three months demonstrated a

significantly greater improvement in laryngeal appearance and

LPR symptoms.

aryngopharyngeal reflux (LPR) has had a significantly

increasing impact on otolaryngologist office visits in

the last decade. In the three-year period 1990-1993, annual

visits to otolaryngologists by patients suffering from reflux-

related problems averaged 89,000; this average increased to

421,000 annual visits during the three-year time span 1998-

2001

. 1

The generally recommended treatment in patients

with LPR is twice-daily-dose proton pump inhibitor (PPI)

therapy for three to six months

. 2,3

However, there is some

controversy regarding the adequate PPI dosage and even the

efficacy of these drugs for LPR treatment

. 3,4

Some authors

criticize these recommendations for LPR treatment as being

based on poor levels of evidence from uncontrolled studies

. 5

In addition, several studies in the past could not demonstrate

superiority of PPIs over placebo for treatment of suspected

LPR

. 6-9

Therefore, the primary objective of this prospec-

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

study was to evaluate the effect of a three-month treatment

with esomeprazole 20 mg twice daily on symptoms and

laryngeal signs in patients with suspected LPR. We chose

esomeprazole for this study as we could show adequate

measurable acid suppression with a once-daily dose of this

PPI in a large number of LPR patients in a former tria

l 4

and

because esomeprazole provides greater 24-hour control of

intragastric acid than all other available PPIs at standard

doses used to treat erosive esophagitis

. 10

MATERIALS AND METHODS

The following procedures were performed in accordance

with the Declaration of Helsinki, Good Clinical Practice,

and applicable regulatory requirements. The study was ap-

proved by the Ethics Committee of the Medical Faculty of

Ludwig Maximilians University Munich (project number

265-05). Before initiation of any procedure, signed in-

formed consent was obtained from all patients.

Participants

Between February 2006 and July 2007, 62 consecutive

patients (30 women and 32 men; age range, 21-77 years;

mean, 48.7 years) were enrolled. They presented to the

Department of Otorhinolaryngology–Head and Neck Sur-

gery of Ludwig Maximilians University, Munich, with un-

specific otolaryngologic and respiratory disorders such as

chronic cough, dysphagia, throat clearing, globus sensation,

hoarseness, sore throat, and heartburn. All patients were

examined by one otolaryngologist and rigid or flexible la-

ryngoscopy had to reveal mucosal abnormalities consistent

with LPR reflected by a reflux finding score (RFS) 7

. 11

addition, the reflux symptom index (RSI)

, 12

a self-adminis-

tered nine-item outcomes instrument for the diagnosis of

LPR, had to exceed the value of 13 for inclusion. None of

the study patients were treated with PPIs or any other

antireflux medication for at least three months. Further

Received April 9, 2008; revised May 27, 2008; accepted June 3, 2008.

Otolaryngology–Head and Neck Surgery (2008) 139, 414-420

doi:10.1016/j.otohns.2008.06.003

Reprinted by permission of Otolaryngol Head Neck Surg. 2008; 139(3):414-420.

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