Clinical trial NCT04657549: Tonsil Surgery in Recurrent or Chronic Tonsillitis
Official title: Partial or Total Surgical Removal of Palatal Tonsils to Change Quality of Life for Adults With Chronic or Recurrent Tonsillitis: Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tonsillitis Recurrent
Tonsillitis Chronic
Keywords: tonsillitis
tonsillectomy
tonsillotomy
tonsil surgery
Lead sponsor: Oulu University Hospital
Sponsor class: OTHER
First posted: 2020-12-08
Enrollment: 147
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Tonsil surgery is common in adults with recurrent or chronic tonsillitis. The surgical techniques include either partial or total surgical removal of the palatal tonsils (tonsillotomy, TT, and tonsillectomy, TE, respectively). The aim of this study is to find out, whether tonsil surgery improves the quality of life in these patients and whether the lighter TT is as effective as TE. Our main outcome is the disease-specific Tonsillectomy Outcome Inventory-14 (TOI-14) quality of life questionnaire score at 6 months follow-up.

Detailed description: Rationale

Surgical removal of palatal tonsils is among the most common ear, nose and throat operations in adults in Finland. The vast majority of these operations are done for recurrent and chronic tonsillitis. Internationally accepted guidelines for the treatment of these diseases are lacking and the indications for tonsil surgery are practice-based rather than evidence-based. The choice of the surgical technique further confuses the picture. The traditional surgical technique has been the total removal of tonsils (tonsillectomy, TE). The relatively recent introduction of partial resection of tonsils, namely tonsillotomy (TT), is suggested to have the benefits of less postoperative pain and smaller risk of post-operative hemorrhage as compared to TE. The relative efficacy of these two techniques to alleviate infective tonsillar diseases is still unclear.

Objectives

The main aim of this study is to obtain reliable evidence on, whether tonsil surgery improves the quality of life in adult patients suffering from recurrent or chronic tonsillitis, and whether the lighter TT would be as effective as TE. We will also compare the scores of a generic quality of life questionnaire as well as several other subjective and objective beneficial and harmful outcomes between the groups.

Methods

In this pragmatic multi-center randomized controlled trial, adult patients suffering from recurrent or chronic tonsillitis will be randomly allocated to three groups: tonsillotomy group (TT), tonsillectomy group (TE) and control group with watchful waiting (WW) in ratio 2:2:1. The patients in the surgical groups are blinded to the operation type (TT or TE). Our hypothesis is that both surgical treatments are more effective than watchful waiting in enhancing quality of life without significant risks (superiority assumption) and that TT is non-inferior to TE when the surgical groups are compared (non-inferiority assumption). Our principal outcome is disease-specific quality of life questionnaire score (Tonsillectomy Outcome Inventory (TOI)-14) at 6 months follow-up. We have validated this questionnaire in Finnish and explored the interpretation of the scores. Secondary outcomes have been listed in the Outcomes section.

Separate random allocation lists for the main research center (Oulu University Hospital) and for the four other centers collectively as well as for recurrent and for chronic tonsillitis will be used. Random permuted blocks is used with block size varying between 5 and 10. Based on our earlier study, the principal outcome, TOI-14 score, will most probably be left-truncated at zero and right-skewed. Therefore, both tobit-analysis and covariate analysis is used with log (1+y) transformation. The primary analysis has two phases. Firstly, the TOI-14 score in the combined surgical group (TT+TE) is compared to that in the WW group. Secondly, the score in the TT group is compared to that in the TE group. Effects will be estimated by adjusted mean differences in the log-transformed scores with 95% confidence intervals. Based on our earlier observational studies on the subject, the following covariates are included in the multivariable adjusted model: gender and baseline TOI-14 score together with stratification factors: enrolling center (Oulu vs. others) and main complaint (recurrent vs. chronic tonsillitis). In case there is missing data on the primary outcome, a multiple imputation method will be used. The analyses will be performed on an intention to treat basis. Per protocol analysis will be performed as sensitivity analysis and results from comparisons on secondary outcomes and subgroup analysis (main complaint) are used to generate hypothesis for future trials.

Eligibility criteria: The inclusion criteria are:

* Recurrent tonsillitis episodes:

  * At least 4 episodes in the previous 12 months or at least 3 episodes in 6 months
  * Episodes are disabling, prevent normal functioning and are severe enough for the patient to seek medical attention
  * Episodes are thought to involve the palatine tonsils based on signs found during the episodes (e.g. edema, erythema, exudative tonsillitis, anterior cervical lymphadenitis)
  * No throat cultures or antigen/molecular tests to show infection with group A streptococcus are needed
* Chronic tonsillitis:

  * Recurrent or chronic throat pain for at least 6 months
  * At least one symptom or sign that indicate that symptoms originate from the palatal tonsils (disturbing tonsil stones, halitosis, anterior cervical lymphadenitis, tonsillar exudates, abnormal tonsillar crypts)
  * Symptomatic treatment has not been effective

The exclusion criteria are:

* Age less than 18 years
* Pregnancy
* History of peritonsillar abscess
* Previous illness that make prompt same-day surgery unfeasible
* No electronic identity verification tools

Primary outcomes:
measure: Tonsillectomy Outcome Inventory -14 (TOI-14) follow-up score
timeFrame: At the end of five to six months follow-up
Secondary outcomes:
measure: 36-Item short Form Survey (SF-36, RAND-36) follow-up score
timeFrame: At the end of five to six months follow-up
measure: Proportion benefiting
timeFrame: At the end of five to six months follow-up
measure: Days with throat pain
timeFrame: At the end of five to six months follow-up
measure: Days with halitosis
timeFrame: At the end of five to six months follow-up
measure: Days with bleeding
timeFrame: At the end of five to six months follow-up
measure: Days with tonsil stones
timeFrame: At the end of five to six months follow-up
measure: Days with absence from work
timeFrame: At the end of five to six months follow-up
measure: Days with dexketoprofen
timeFrame: At the end of five to six months follow-up
measure: Days with acetaminophen
timeFrame: At the end of five to six months follow-up
measure: Days with oxycodone/naloxone
timeFrame: At the end of five to six months follow-up
measure: Medical visits
timeFrame: At the end of five to six months follow-up
measure: Antibiotic courses
timeFrame: At the end of five to six months follow-up
measure: Adverse effect-postoperative bleeding
timeFrame: At the end of five to six months follow-up
measure: Adverse effect - postoperative pain
timeFrame: At the end of five to six months follow-up
measure: Adverse effect - postoperative infection
timeFrame: At the end of five to six months follow-up
measure: Adverse effect - dental injury
timeFrame: At the end of five to six months follow-up
measure: Adverse effect -anesthetic complication
timeFrame: At the end of five to six months follow-up
measure: Adverse effect - tightness/globus
timeFrame: At the end of five to six months follow-up
measure: Adverse effect - voice problems
timeFrame: At the end of five to six months follow-up
measure: Adverse effect - jaw problems
timeFrame: At the end of five to six months follow-up
Other outcomes:
Locations:
city: Rovaniemi
country: Finland
facility: Lapland Central Hospital
state: Lapland
city: Kemi
country: Finland
facility: Länsi-Pohja Central Hospital
city: Kokkola
country: Finland
facility: Keski-Pohjanmaa Central Hospital
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Seinäjoki
country: Finland
facility: Seinäjoki Central Hospital
city: Turku
country: Finland
facility: Turun yliopistollinen keskussairaala
city: Vaasa
country: Finland
facility: Vaasan keskussairaala
Study officials:
affiliation: Oulu University Hospital, University of Oulu
name: Olli-Pekka Alho, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oulu University Hospital, University of Oulu
name: Aleksi EJ Laajala, MD
role: STUDY_CHAIR
affiliation: Oulu University Hospital, University of Oulu
name: Paulus Tokola, MD
role: STUDY_CHAIR
affiliation: Oulu University Hospital
name: Timo J Autio, MD, PhD
role: STUDY_CHAIR
affiliation: University of Oulu
name: Timo J Koskenkorva, MD, PhD
role: STUDY_CHAIR
affiliation: Division of Operative Care, Oulu University Hospital, Finland
name: Pasi Ohtonen, M. Sc.
role: STUDY_CHAIR
affiliation: Oulu University
name: Esa Läärä, PhD.
role: STUDY_CHAIR
References:
citation: Laajala A, Autio TJ, Ohtonen P, Alho OP, Koskenkorva TJ. Interpretation of Tonsillectomy Outcome Inventory-14 scores: a prospective matched cohort study. Eur Arch Otorhinolaryngol. 2020 May;277(5):1499-1505. doi: 10.1007/s00405-020-05832-z. Epub 2020 Feb 14.
citation: Koskenkorva T, Koivunen P, Laara E, Alho OP. Predictive factors for quality of life after tonsillectomy among adults with recurrent pharyngitis: a prospective cohort study. Clin Otolaryngol. 2014 Aug;39(4):216-23. doi: 10.1111/coa.12263.
citation: Laajala A, Tokola P, Autio TJ, Koskenkorva T, Tastula M, Ohtonen P, Laara E, Alho OP. Total or partial tonsillar resection (tonsillectomy or tonsillotomy) to change the quality of life for adults with recurrent or chronic tonsillitis: study protocol for a randomised controlled trial. Trials. 2021 Sep 15;22(1):617. doi: 10.1186/s13063-021-05539-4.