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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
120
A 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.
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.
Tampere University Hospital
Tampere, Finland
RECRUITINGChange from baseline Sino-Nasal Outcome Test (SNOT-22) score at 3 months
The effect of balloon sinuplasty treatment in chronic maxillary rhinosinusitis is measured primarily with the Sino-Nasal Outcome Test (SNOT-22). The Sino-Nasal Outcome Test (SNOT-22) is a patient-reported measure of outcome developed for use in chronic rhinosinusitis with or without nasal polyposis. It can be used to assess the impact of chronic rhinosinusitis on the patient's quality of life. It may also be used to measure the outcome of a surgical intervention (Hopkins et al. 2009). In this study, SNOT-22 translated in Finnish is used. The validation of the Finnish version has been made by the Finnish Medical Society Duodecim.
Time frame: Patients fill the SNOT-22-questionnaire preoperatively and 3 months post-operative
Change from baseline Sino-Nasal Outcome Test (SNOT-22) score at 6 months
The effect of balloon sinuplasty treatment in chronic maxillary rhinosinusitis is measured primarily with the Sino-Nasal Outcome Test (SNOT-22). The Sino-Nasal Outcome Test (SNOT-22) is a patient-reported measure of outcome developed for use in chronic rhinosinusitis with or without nasal polyposis. It can be used to assess the impact of chronic rhinosinusitis on the patient's quality of life. It may also be used to measure the outcome of a surgical intervention (Hopkins et al. 2009). In this study, SNOT-22 translated in Finnish is used. The validation of the Finnish version has been made by the Finnish Medical Society Duodecim.
Time frame: Patients fill the SNOT-22-questionnaire preoperatively and 6 months post-operative
Change from baseline Sino-Nasal Outcome Test (SNOT-22) score at 9 months
The effect of balloon sinuplasty treatment in chronic maxillary rhinosinusitis is measured primarily with the Sino-Nasal Outcome Test (SNOT-22). The Sino-Nasal Outcome Test (SNOT-22) is a patient-reported measure of outcome developed for use in chronic rhinosinusitis with or without nasal polyposis. It can be used to assess the impact of chronic rhinosinusitis on the patient's quality of life. It may also be used to measure the outcome of a surgical intervention (Hopkins et al. 2009). In this study, SNOT-22 translated in Finnish is used. The validation of the Finnish version has been made by the Finnish Medical Society Duodecim.
Time frame: Patients fill the SNOT-22-questionnaire preoperatively and 9 months post-operative
Change from baseline Sino-Nasal Outcome Test (SNOT-22) score at 12 months
The effect of balloon sinuplasty treatment in chronic maxillary rhinosinusitis is measured primarily with the Sino-Nasal Outcome Test (SNOT-22). The Sino-Nasal Outcome Test (SNOT-22) is a patient-reported measure of outcome developed for use in chronic rhinosinusitis with or without nasal polyposis. It can be used to assess the impact of chronic rhinosinusitis on the patient's quality of life. It may also be used to measure the outcome of a surgical intervention (Hopkins et al. 2009). In this study, SNOT-22 translated in Finnish is used. The validation of the Finnish version has been made by the Finnish Medical Society Duodecim.
Time frame: Patients fill the SNOT-22-questionnaire preoperatively and 12 months post-operative
Change from baseline in the number of acute rhinosinusitis infections at 3 months
In recurrent acute maxillary rhinosinusitis, the effect of balloon sinuplasty treatment is measured primarily with the change in number of acute rhinosinusitis infections. It is hard to measure the effect of the balloon sinuplasty in recurrent acute rhinosinusitis with methods questioning the current state of disease, because patients are asymptomatic between episodes of sinusitis. That is why the patients are asked the number of maxillary rhinosinusitis during the last 3 months preoperatively and that number is compared to the number of postoperative maxillary rhinosinusitis asked at 3 months after the operation.
Time frame: Preoperative and 3 months post-operative
Change from baseline in the number of acute rhinosinusitis infections at 6 months
In recurrent acute maxillary rhinosinusitis, the effect of balloon sinuplasty treatment is measured primarily with the change in number of acute rhinosinusitis infections. It is hard to measure the effect of the balloon sinuplasty in recurrent acute rhinosinusitis with methods questioning the current state of disease, because patients are asymptomatic between episodes of sinusitis. The patients are asked the number of maxillary rhinosinusitis during the last 6 months preoperatively and that number is compared to the number of postoperative maxillary rhinosinusitis that the patients have had during the post-operative 6 months.
Time frame: Preoperative and 6 months post-operative
Change from baseline in the number of acute rhinosinusitis infections at 12 months
In recurrent acute maxillary rhinosinusitis, the effect of balloon sinuplasty treatment is measured primarily with the change in number of acute rhinosinusitis infections. It is hard to measure the effect of the balloon sinuplasty in recurrent acute rhinosinusitis with methods questioning the current state of disease, because patients are asymptomatic between episodes of sinusitis. The patients are asked the number of maxillary rhinosinusitis during the last 12 months preoperatively and that number is compared to the number of postoperative maxillary rhinosinusitis infections that the patients have had during the post-operative 12 months.
Time frame: Preoperative and 12 months post-operative
Amount of sick leaves
The number of sick leaves during the last year, last 6 and last 3 months is asked preoperatively, focusing on the sick leaves that are caused because of chronic or recurrent rhinosinusitis. Also, the information about the postoperative sick leaves is collected during all the controls in order to find out whether the amount of sick leaves changes after the operation or not.
Time frame: Preoperative and 3, 6, 9 and 12 months post-operative
Number of antibiotic treatments needed
One way to estimate the effectiveness of balloon sinuplasty is to collect the data of antibiotic treatments. Especially in the cases of recurrent acute rhinosinusitis this is valid information. In this study, the number of antibiotic treatments during the last year, last 6 and last 3 months is checked from the Prescription Centre. Also, the information about the postoperative antibiotic treatments is collected during all the controls from the Prescription Centre in order to find out whether the amount of antibiotic treatments changes after the operation or not.
Time frame: Preoperative and 3, 6, 9 and 12 months post-operative
Eustachian Tube Dysfunction Questionnaire (ETDQ-7)
Eustachian tube dysfunction is a common condition which causes ear symptoms such as clogging and popping. The condition is also commonly associated with chronic sinusitis. The ETDQ-7 is a valid and reliable symptom score for use in adult patients with Eustachian tube dysfunction. It is a 7-item questionnaire which inquires patient´s ear symptoms. It is easily administered in the clinical setting and has minimal burden to respondents (McCoul et al. 2012). In this study ETDQ-7 is used to evaluate patient´s possible ear symptoms which refer to Eustachian tube dysfunction. Patients fill the ETDQ-7-questionnaire preoperatively and during all the controls.
Time frame: Preoperative and 3, 6, 9 and 12 months post-operative
Visual Analog Scale (VAS)
A Visual Analogue Scale (VAS) is a measurement instrument that tries to measure a characteristic or attitude that is believed to range across a continuum of values and cannot easily be directly measured. Operationally a VAS is usually a horizontal line, 100 mm in length, anchored by word descriptors at each end. The patient marks on the line the point that they feel represents their perception of their current state. The VAS score is determined by measuring in millimetres from the left-hand end of the line to the point that the patient marks (Wewers and Lowe 1990). In this study, VAS is used to measure the symptoms of nasal obstruction, nasal discharge, facial pain/pressure and olfactory disorder. Patients report their symptoms preoperatively and during all the controls.
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Time frame: Preoperative and 3, 6, 9 and 12 months post-operative
The clinical status of nasal mucosa in nasal endoscopy assessed in terms of mucosal oedema, nasal discharge and synechiae
Nasal endoscopy involves evaluation of the nasal and sinus passages with direct vision. It is a commonly performed procedure in the otolaryngology and serves as an objective diagnostic tool in the evaluation of nasal mucosa, sinonasal anatomy, and nasal pathology. During the diagnostic nasal endoscopy, a patient is always awake and seated upright in a chair. A local anaesthetic lidocaine spray is applied to the nose to make insertion of the endoscope less uncomfortable. In this study, nasal endoscopy is done to assess nasal mucosa preoperatively and during postoperative visits at 3 and 12 months. Mucosal oedema, nasal discharge and synechiae are documented and reported either "Yes" or "No". A special attention is paid on the findings in the middle meatus of the nose.
Time frame: Preoperative and during post-operative visits at 3 and 12 months
Signs of Eustachian tube dysfunction in otomicroscopic ear status
In clinical examination, preoperatively and during the control visits at 3 and 12 months, a special attention is paid on the otomicroscopic ear status in order to find out signs of Eustachian tube dysfunction, such as tympanic membrane retraction and middle ear effusion. The tympanic membrane retraction and the presence of middle ear effusion are categorized either "Yes" or "No" and evaluated for both ears separately. Valsalva and Toynbee tests are also performed during the examination and documented either "positive" or "negative" for both ears separately.
Time frame: Preoperative and during post-operative visits at 3 and 12 months
Inspiratory nasal resistance in Rhinomanometry
Rhinomanometry measures the nasal airway resistance and flow. It is a tool for determining the degree of airflow obstruction before and after surgical procedures and medical interventions. It may also help to distinguish functional causes of upper airway obstruction from structural causes (Clement et al. 2014). Active anterior rhinometry is the most commonly used method and it is performed as follows: One nostril is closed with an adhesive tape, pierced by the catheter for pressure determination, and a mask covers the nose and the mouth. The pressure flow curve is recorded with a storage oscilloscope and projected onto a pre-printed diagram. In this study, the rhinomanometry is used to evaluate the possible effect of balloon sinuplasty procedure on the nasal airway resistance. The total inspiratory nasal resistance is measured as well as the resistance in right and left nostrils separately. The measurement is carried out preoperatively and during the control visits at 3 and 12 months.
Time frame: Preoperative and during post-operative visits at 3 and 12 months
Signs of Eustachian tube dysfunction in Tympanometry
In tympanometry, middle ear pressure is measured with an electroacoustic impedance meter that allows the precise evaluation of eardrum mobility and helps to assess Eustachian tube function. The tympanometric curves are traditionally classified as follows (Lidén 1969; Jerger 1970): type A, normal ET function; type B, flat tympanogram characteristic of the presence of fluid in the middle ear or eardrum perforation; or type C, peak at very negative pressure, typically 150 dPa, which may be indicative of eardrum retraction and Eustachian tube dysfunction. Tympanometric peak pressure is the peak admittance in the tympanogram and an indirect measurement of middle ear pressure. In this study, the tympanometric peak pressure is measured and the type of tympanometric curve is recorded from both ears separately. The measurement is carried out preoperatively and during the control visits at 3 and 12 months.
Time frame: Preoperative and during post-operative visits at 3 and 12 months
The opening of Eustachian tube in Tubomanometry
The principle of tubomanometry is to deliver defined pressures of 30, 40 and 50 mbar to the epipharynx through a nasal applicator. If the Eustachian tube opens during swallowing, the defined pressure applied to the epipharynx is transmitted to the middle ear and the pressure change can be registered in the external auditory canal. In this study the opening latency index (R-value) is recorded in pressures of 30, 40 and 50 mbar for both ears separately and also the information, whether the Eustachian tube opened or not in those pressures. The opening latency index (R-value) reflects the latency between pressure application in the epipharynx and measurement of a pressure change in the ear canal. An immediate opening (R \< 1) indicates normal ET function and a late opening (R ≥ 1) indicates restricted ET function. No opening (R negative or not measurable) indicates complete obstruction of the ET (Schröder et al. 2015).
Time frame: Preoperative and during post-operative visits at 3 and 12 months
Change from baseline in Lund-Mackay score at 12 months measured from the Cone Beam Computed Tomography (CBCT) scans
Cone Beam Computed Tomography (CBCT) is an X-ray based volume acquisition method providing 3D images of the head. In this study CBCT is used preoperatively in the diagnostics of chronic rhinosinusitis in patient selection. Another CBCT scan is taken during the control visit at 12 months. The radiological staging (Lund-Mackay score) of the chronic sinusitis is graded from the CBCT scans both preoperatively and postoperatively. When evaluating a CBCT scan of the paranasal sinuses and ostiomeatal complex, the researcher assigns each sinus a score of: 0 (no abnormality), 1 (partial opacification) or 2 (complete opacification).The ostiomeatal complex is assigned a score of either 0 (not obstructed) or 2 (obstructed). Each side is graded separately. A combined score of up to 24 is possible.
Time frame: Preoperative and 12 months post-operative
Volumetric measurements with OnDemand3D™ software analyzed from Cone Beam Computed Tomography (CBCT) scans
Cone Beam Computed Tomography (CBCT) is an X-ray based volume acquisition method providing 3D images of the head. In this study CBCT is used preoperatively in the diagnostics of chronic rhinosinusitis in patient selection. Another CBCT scan is taken during the control visit at 12 months. Volumetric measurements of the sinuses, infundibuli and ostia will be made from the scans both preoperatively and postoperatively. Volumetric measurements are performed with OnDemand3D™ software (version 1.0, CyberMed, Inc., Yuseong-gu, Daejeon, South Korea) which has been used for similar purpose in a previous study (Valtonen et al. 2018). In accordance with the previous study, the same Hounsfield Unit (HU) values from -1000 to -430 in CBCT scans are utilized to define air in nose for volumetric measurements.
Time frame: Preoperative and 12 months post-operative
Nasal mucosal biopsy
Nasal mucosal biopsy is taken from the anterior head of both middle turbinates in local anaesthesia in the beginning of the operations and during the post-operative visit at 12 months. In local anaesthesia a local anaesthetic (Lidocain 10mg/ml c. adrenalin, Orion, Finland) is applied to the anterior head of the middle turbinate. All the specimens are examined by a pathologist. The main purpose of the examination is to compare preoperative and post-operative mucosal specimens and evaluate the effect of balloon sinuplasty treatment on the degree of inflammation in the nasal cavity.
Time frame: In the operation and 12 months post-operative