Clinical trial NCT04645511: Balloon Sinuplasty Efficiency in Maxillary Rhinosinusitis.
Official title: A Placebo Controlled Randomised Study of the Balloon Sinuplasty Efficiency in Chronic or Recurrent Maxillary Rhinosinusitis.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Maxillary Sinusitis
Sinusitis, Chronic
Sinusitis Recurrent
Eustachian Tube Dysfunction
Keywords: Balloon sinuplasty
Lead sponsor: Tampere University Hospital
Sponsor class: OTHER
First posted: 2020-11-27
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A prospective, randomized, placebo-controlled, double-blinded clinical study
Primary purpose: TREATMENT

Brief summary: This study is a prospective, randomized, placebo-controlled, double-blinded clinical study. The balloon sinuplasty treatment is compared to placebo effect in chronic or recurrent maxillary sinusitis. The purpose is to find out the efficacy of balloon sinuplasty of maxillary sinuses and the patients who get the best benefit from balloon sinuplasty. The investigators also want to find out if balloon sinuplasty of maxillary sinuses improves Eustachian tube dysfunction. The study is executed in the Department of Ear and Oral Diseases, Tampere University Hospital. 120 patients who have either recurrent acute or chronic rhinosinusitis without nasal polyposis and whose sinusitis is limited mainly into maxillary sinuses, are recruited in the study. The patients are allocated either into the chronic maxillary sinusitis (60 patients) or the recurrent maxillary sinusitis (60 patients) branch of the study. Then, the patients are consecutively randomized into two treatment groups in the proportion of 1 to 1: A) Balloon sinuplasty group and B) Placebo group. The treatment is performed according to the patient's group status and all the patients are followed 12 months postoperatively.

The effect of balloon sinuplasty treatment in chronic maxillary rhinosinusitis is going to be measured primarily with the Sino-Nasal Outcome Test (SNOT-22). In recurrent acute maxillary rhinosinusitis, the effect of balloon sinuplasty treatment will be measured primarily with the number of acute rhinosinusitis infections. Besides this, number of antibiotic treatments and sick leaves are inquired, Visual Analog Scale (VAS) and Eustachian Tube Dysfunction Questionnaire (ETDQ-7) are used, rhinomanometry, Cone Beam Computed Tomography (CBCT), tympanometry, tubomanometry, nasal endoscopy and general evaluation of the patients clinical ORL-status are performed. Also pre- and postoperative biopsies are taken from the middle turbinates.

Detailed description: This study is a prospective, randomized, placebo-controlled, double-blinded clinical study. The purpose of the study is to compare the balloon sinuplasty treatment to placebo effect in chronic or recurrent maxillary sinusitis and to find out the efficacy of balloon sinuplasty in different stages of rhinosinusitis (recurrent vs. chronic). The goal is to find out the patients who get the best benefit from balloon sinuplasty. The investigators also want to find out if balloon sinuplasty of maxillary sinuses improves Eustachian tube dysfunction.

The study is executed in the Department of Ear and Oral Diseases, Tampere University Hospital. 120 patients who have either recurrent acute or chronic rhinosinusitis without nasal polyposis and whose sinusitis is limited mainly into maxillary sinuses, are recruited in the study. After the first visit, when the patient has filled the consent form and all the preoperative evaluation has been carried out, the examining doctor sends the patient's study number and all the information needed for the randomization and allocation to a person who carries out the randomization and does not know anything else about the patient and does not participate in the examination or the treatment of the patients. The patients are allocated either into the chronic maxillary sinusitis (60 patients) or the recurrent maxillary sinusitis (60 patients) branch of the study. Then, the patients are consecutively randomized into two treatment groups in the proportion of 1 to 1 by using MINIM, an MS-DOS program that randomizes patients to treatment groups by the method of minimization. The treatment groups are A) Balloon sinuplasty group and B) Placebo group (sham surgery).

Sample size calculation was based on comparison of proportions between two independent samples. It was estimated that the balloon sinuplasty could improve the situation of approximately 60% of the chronic rhinosinusitis patients. There is a likely placebo effect in the sham surgery group and therefore it was estimated that the situation in 20% of the patients in that group could significantly be improved. When using alfa = 0.05, power = 0.80 and the proportion difference of 60% vs. 20%, the calculation showed that 27 + 27 observations are needed. This was rounded up to final sample of 30 patients in the balloon sinuplasty group and 30 patients in the placebo group. Similar benefits of balloon sinuplasty were assumed concerning recurrent acute maxillary rhinosinusitis and therefore the final sample size would also be 30 patients in the balloon sinuplasty group and 30 patients in the placebo group. The total sample size will therefore be 120 patients.

The treatment is performed in similar circumstances for both the balloon sinuplasty and the placebo group in the day surgery section of the ENT clinic. The staff of the day surgery section is instructed to avoid any kind of communication, before and during the operation as well as during the post-operative care, which might reveal the group of the patient. The operation theatre nurses open the sealed randomization envelope and prepare the room according to it. All the surgical devices to be used in the operation are hidden under a sterile linen when the patient enters the room. Before the operation begins, the patient is set on the operation table and his/her eyes are covered with moist gauze dressing pads. The operating doctor reads the randomization group status information from the envelope, which tells whether the operation is going to be a balloon sinuplasty or a placebo procedure, in the operation theatre just before the operation.

The operations are carried out in local anesthesia which is always performed similarly for both groups. Topical anesthesia is performed for each patient. All the procedures are performed under a direct vision of a straight, 4mm diameter, 0-degree endoscope. Operation time and possible bleeding and pain during the operation are documented. Nasal mucosal biopsies are taken from the anterior portions of middle turbinates from all the patients. Then in the Balloon sinuplasty group the balloon sinuplasty operation is performed: the shapeable tip of the balloon dilatation device (Entellus XprESS LoProfile; Stryker Corporation, Kalamazoo, Michigan, U.S.A.), with maxillary bending, is inserted into the maxillary sinus ostium. Then guided with the tip, a flexible balloon (6 mm x 20 mm) is gently inserted into the ostium and inflated up to 12 atm for 15 seconds. The dilatation is repeated one more time. The same procedure is performed for both maxillary sinuses. In the placebo treatment group the middle meatus is gently palpated with a curved suction tip (the tip is not connected to a suction unit). The curved suction tip is placed medial to the uncinate process. In order to create a better placebo effect, the operating doctor says: "Now inflate the balloon up to 12 atm for 15 seconds." After 15 seconds the doctor says: "Deflate the balloon." This is repeated one more time. Similar procedure is carried out on both sides.

The operating doctor does not participate in the pre- or postoperative evaluation of the patients. The information, whether the patient had a placebo procedure or the balloon sinuplasty procedure, is not written in the patient's medical record. It is only written that the patient had an operation in accordance with the study protocol. The more detailed information of the operation is written on the Surgery form and the form is sealed in an envelope and the envelope is sent to the study nurse, who stores it inside a locked filing cabinet in her locked office. The envelope is only opened in the end of the 12-month follow-up visit.

The examining doctor follows the patients for the next 12 months after the operation. The follow-up visits take place 3 and 12 months postoperatively. At 6 and 9 months postoperatively, there will be a phone interview by the study nurse and the patients will fill a web based electronic follow-up form. In the end of the 12 month follow-up visit, the examining doctor and the patient are informed about the patient's group status and the patients in the placebo group are given the option to receive the balloon sinuplasty treatment outside the study.

The effect of balloon sinuplasty treatment in chronic maxillary rhinosinusitis will be measured primarily with the Sino-Nasal Outcome Test (SNOT-22), which measures the quality of life and also the outcome of a surgical intervention. In recurrent acute maxillary rhinosinusitis, the effect of balloon sinuplasty treatment will be measured primarily with the number of acute rhinosinusitis infections. Besides this, number of antibiotic treatments and sick leaves are inquired, Visual Analog Scale (VAS) is used, rhinomanometry, nasal endoscopy and general evaluation of the patients clinical ORL-status are performed. Cone Beam Computed Tomography (CBCT) is performed preoperatively and at the 12 month follow-up visit. To measure the Eustachian tube dysfunction, patients are going to fill in the Eustachian Tube Dysfunction Questionnaire (ETDQ-7) and tympanometry and tubomanometry are performed. To estimate the histological effectiveness for rhinal inflammation, pre- and postoperative biopsies are taken from the middle turbinates.

In chronic maxillary rhinosinusitis, the improvement of the quality of life will be analysed with either paired t-test or Wilcoxon rank sum test depending on the shape of the distribution of the SNOT-22 scores. The comparison between the groups regarding the SNOT-22 score change will be carried out with either independent samples T-test or Mann-Whitney test depending on the distribution. In recurrent acute maxillary rhinosinusitis, the reduction of sinusitis episodes and comparison between two groups will be analysed with Fisher exact test.

The results of this study will be submitted for publication to peer reviewed international journals.

The Pirkanmaa Hospital District and the research group with its grants bear the expenses of the study. The researchers are not payed for executing the study but they will apply for grants.

Eligibility criteria: Inclusion Criteria:

* Patients at least 18 years old and younger than 70 years old
* Patients willing to participate in the study
* Patients whose diseases fill the definitions of chronic or acute recurrent maxillary rhinosinusitis
* Patients with chronic maxillary rhinosinusitis has not responded to a 3-month trial of topical corticosteroid treatment
* SNOT-22 points 8 or more in chronic maxillary rhinosinusitis
* In recurrent acute maxillary rhinosinusitis, no SNOT-22 point limits are used
* Modified Lund-Mackay inclusion criteria in chronic rhinosinusitis group:

  1. Maxillar 0-2
  2. Anterior Ethmoid 0-2
  3. Posterior Ethmoid 0-1
  4. Sphenoid 0-1
  5. Frontal 0-1
  6. Ostiomeatal complex 0 or 2

Exclusion Criteria:

* Chronic rhinosinusitis with nasal polyps
* Notable inflammation in the ethmoidal, sphenoidal or frontal sinuses along with maxillary sinusitis
* Previous nasal surgery
* Sinonasal tumor
* Maxillary rhinosinusitis caused by a dental problem
* Facial pain caused by other etiologies
* Cystic fibrosis
* Gross immunodeficiency
* Congenital mucociliary problems
* Non-invasive fungal balls and invasive fungal disease
* Systemic vasculitis and granulomatous disease
* Severe systemic diseases
* Malignancies
* Pregnancy

Definitions:

Recurrent acute maxillary rhinosinusitis:

* 4 or more episodes (\< 12 weeks) of acute rhinosinusitis with typical symptoms per year and no persistent symptoms between the rhinosinusitis episodes (Chan and Kuhn 2009)
* The diagnosis of the recurrent episodes of acute rhinosinusitis have been made with the following criteria:

  * Increase of symptoms after 5 days or persistent symptoms after 10 days and
  * During the episode, 2 or more symptoms, one of which should be either nasal blockage/obstruction or nasal discharge (anterior/posterior nasal drip)
  * +/- facial pain/pressure
  * +/- reduction or loss of smell (Fokkens et al. 2012) and either
  * Signs of mucopurulent discharge primarily from the middle meatus seen in anterior rhinoscopy or nasoendoscopy and/or
  * Oedema/mucosal obstruction primarily seen in the middle meatus in anterior rhinoscopy or nasoendoscopy and/or
  * Signs of mucopurulent discharge seen in the nasopharynx or posterior oropharynx and/or
  * Signs of acute maxillary sinusitis is seen in sinus X-rays or CT/CBCT scans and/or
  * Signs of acute maxillary sinusitis seen in the sinus ultrasound
* No signs of mucosal disease at nasoendoscopy during the asymptomatic period
* At most, minor signs of inflammation in the maxillary sinuses and/or ostiomeatal complex in CT/CBCT scans during the asymptomatic period

  * Maximum 2-3 mm mucosal thickness in maxillary sinus medial and lateral wall

Chronic maxillary rhinosinusitis:

* Presence of typical symptoms of chronic rhinosinusitis for equal or longer than 12 weeks

  * 2 or more symptoms, one of which should be either nasal blockage/obstruction or nasal discharge (anterior/posterior nasal drip)
  * +/- facial pain/pressure
  * +/- reduction or loss of smell and either
  * Endoscopic signs of mucopurulent discharge primarily from middle meatus and/or
  * Endoscopic signs of oedema/mucosal obstruction primarily in middle meatus and/or
  * Inflammatory mucosal changes within the ostiomeatal complex and/or sinus in the CT/CBCT scans and the changes are limited mainly into maxillary sinuses (Fokkens et al. 2012)

The patients are not recruited in the study while they are having an exacerbation of chronic rhinosinusitis or an ongoing acute rhinosinusitis. Neither are the follow-up visits carried out during these episodes but postponed later. This way it can be ensured that the preoperative evaluation and the follow-up evaluation correspond with each other.

Primary outcomes:
measure: Change from baseline Sino-Nasal Outcome Test (SNOT-22) score at 3 months
timeFrame: Patients fill the SNOT-22-questionnaire preoperatively and 3 months post-operative
measure: Change from baseline Sino-Nasal Outcome Test (SNOT-22) score at 6 months
timeFrame: Patients fill the SNOT-22-questionnaire preoperatively and 6 months post-operative
measure: Change from baseline Sino-Nasal Outcome Test (SNOT-22) score at 9 months
timeFrame: Patients fill the SNOT-22-questionnaire preoperatively and 9 months post-operative
measure: Change from baseline Sino-Nasal Outcome Test (SNOT-22) score at 12 months
timeFrame: Patients fill the SNOT-22-questionnaire preoperatively and 12 months post-operative
measure: Change from baseline in the number of acute rhinosinusitis infections at 3 months
timeFrame: Preoperative and 3 months post-operative
measure: Change from baseline in the number of acute rhinosinusitis infections at 6 months
timeFrame: Preoperative and 6 months post-operative
measure: Change from baseline in the number of acute rhinosinusitis infections at 12 months
timeFrame: Preoperative and 12 months post-operative
Secondary outcomes:
measure: Amount of sick leaves
timeFrame: Preoperative and 3, 6, 9 and 12 months post-operative
measure: Number of antibiotic treatments needed
timeFrame: Preoperative and 3, 6, 9 and 12 months post-operative
measure: Eustachian Tube Dysfunction Questionnaire (ETDQ-7)
timeFrame: Preoperative and 3, 6, 9 and 12 months post-operative
measure: Visual Analog Scale (VAS)
timeFrame: Preoperative and 3, 6, 9 and 12 months post-operative
measure: The clinical status of nasal mucosa in nasal endoscopy assessed in terms of mucosal oedema, nasal discharge and synechiae
timeFrame: Preoperative and during post-operative visits at 3 and 12 months
measure: Signs of Eustachian tube dysfunction in otomicroscopic ear status
timeFrame: Preoperative and during post-operative visits at 3 and 12 months
measure: Inspiratory nasal resistance in Rhinomanometry
timeFrame: Preoperative and during post-operative visits at 3 and 12 months
measure: Signs of Eustachian tube dysfunction in Tympanometry
timeFrame: Preoperative and during post-operative visits at 3 and 12 months
measure: The opening of Eustachian tube in Tubomanometry
timeFrame: Preoperative and during post-operative visits at 3 and 12 months
measure: Change from baseline in Lund-Mackay score at 12 months measured from the Cone Beam Computed Tomography (CBCT) scans
timeFrame: Preoperative and 12 months post-operative
measure: Volumetric measurements with OnDemand3D™ software analyzed from Cone Beam Computed Tomography (CBCT) scans
timeFrame: Preoperative and 12 months post-operative
measure: Nasal mucosal biopsy
timeFrame: In the operation and 12 months post-operative
Other outcomes:
measure: Adverse events
timeFrame: 3, 6, 9 and 12 months post-operative
measure: General evaluation of the patient and clinical ORL-status
timeFrame: Preoperative and during post-operative visits at 3 and 12 months
Locations:
city: Tampere
country: Finland
facility: Tampere University Hospital
Study officials:
affiliation: Professor
name: Markus Rautiainen, Professor
role: STUDY_CHAIR
affiliation: Doctoral thesis researcher
name: Johanna Luukkanen, MD
role: PRINCIPAL_INVESTIGATOR
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citation: Schroder S, Lehmann M, Korbmacher D, Sauzet O, Sudhoff H, Ebmeyer J. Evaluation of tubomanometry as a routine diagnostic tool for chronic obstructive Eustachian tube dysfunction. Clin Otolaryngol. 2015 Dec;40(6):691-7. doi: 10.1111/coa.12451.
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