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.
