- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04657549
Tonsil Surgery in Recurrent or Chronic Tonsillitis
Partial or Total Surgical Removal of Palatal Tonsils to Change Quality of Life for Adults With Chronic or Recurrent Tonsillitis: Randomized Controlled Trial.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Aleksi EJ Laajala, MD
- Phone Number: +358505794360
- Email: aleksi.laajala@ppshp.fi
Study Contact Backup
- Name: Paulus Tokola, MD
- Phone Number: +358505794281
Study Locations
-
-
-
Kemi, Finland, FIN-94100
- Länsi-Pohja Central Hospital
-
Kokkola, Finland, FIN-67200
- Keski-Pohjanmaa Central Hospital
-
Oulu, Finland, FIN-90029
- Oulu University Hospital
-
Seinäjoki, Finland, FIN-60220
- Seinajoki Central Hospital
-
Turku, Finland
- Turun Yliopistollinen Keskussairaala
-
Vaasa, Finland
- Vaasan keskussairaala
-
-
Lapland
-
Rovaniemi, Lapland, Finland, FIN-96400
- Lapland Central Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Tonsillectomy
Patients will undergo tonsillectomy under general anesthesia within three weeks after enrollment.
|
Tonsillectomy is done by monopolar electrocautery, bipolar scissors or cold instruments.
First the mucosa of the anterior palatinal arch is incised and tonsillar capsule identified, then tonsillar tissue is removed along the capsule.
Any bleeding is coagulated either with monopolar or bipolar electrocautery.
Other Names:
|
Active Comparator: Tonsillotomy
Patients will undergo tonsillotomy under general anesthesia within three weeks after enrollment.
|
Tonsillotomy is done using monopolar electrosurgery, bipolar scissors or coblator device.
Most of the tonsillar tissue is removed, exceeding the removal behind the line between anterior and posterior palatinal arch so that only thin layer of tonsil tissue is left over the tonsillar capsule.
Other Names:
|
No Intervention: Watchful waiting
Patients will be closely monitored for the 5-6 months monitoring period.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tonsillectomy Outcome Inventory -14 (TOI-14) follow-up score
Time Frame: At the end of five to six months follow-up
|
TOI-14 is a disease-specific quality of life questionnaire for throat related symptoms in adults.
TOI-14 summary scores vary between 0 and 100 with higher values indicating poorer quality of life.
Analysis is described in the Detailed Description section.
|
At the end of five to six months follow-up
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
36-Item short Form Survey (SF-36, RAND-36) follow-up score
Time Frame: At the end of five to six months follow-up
|
Difference in RAND-36 domains scores between groups.
RAND-36 instrument produces eight individual values between 0 and 100 (one for each domain), with higher scores indicating better quality of life
|
At the end of five to six months follow-up
|
Proportion benefiting
Time Frame: At the end of five to six months follow-up
|
Difference in proportions of patients benefiting clinically significantly from the intervention between the groups (minimum important change in TOI-14 score)
|
At the end of five to six months follow-up
|
Days with throat pain
Time Frame: At the end of five to six months follow-up
|
Difference in the number of days patients have throat pain (severity scaled 0-10) between the groups
|
At the end of five to six months follow-up
|
Days with halitosis
Time Frame: At the end of five to six months follow-up
|
Difference in the number of days patients have bad breath (severity scaled 0-10) between the groups
|
At the end of five to six months follow-up
|
Days with bleeding
Time Frame: At the end of five to six months follow-up
|
Difference in the number of days patients have bleeding from the throat (severity scaled 0-10) between the groups
|
At the end of five to six months follow-up
|
Days with tonsil stones
Time Frame: At the end of five to six months follow-up
|
Difference in the number of days patients have bothering tonsil stones (severity scaled 0-10) between the groups
|
At the end of five to six months follow-up
|
Days with absence from work
Time Frame: At the end of five to six months follow-up
|
Difference in the number of days patients are absent from work or school due to throat symptoms between the groups
|
At the end of five to six months follow-up
|
Days with dexketoprofen
Time Frame: At the end of five to six months follow-up
|
Difference in the number of days patients take deksketoprofen 25 mg pain medication due to throat pain between the groups
|
At the end of five to six months follow-up
|
Days with acetaminophen
Time Frame: At the end of five to six months follow-up
|
Difference in the number of days patients take acetaminophen 1 g pain medication due to throat pain between the groups
|
At the end of five to six months follow-up
|
Days with oxycodone/naloxone
Time Frame: At the end of five to six months follow-up
|
Difference in the number of days patients take oxycodone/naloxone 5mg/2.5mg
pain medication due to throat pain between the groups
|
At the end of five to six months follow-up
|
Medical visits
Time Frame: At the end of five to six months follow-up
|
Difference in the number of medical visit for throat symptoms between the groups
|
At the end of five to six months follow-up
|
Antibiotic courses
Time Frame: At the end of five to six months follow-up
|
Difference in the number of antibiotic courses for throat symptoms between the groups
|
At the end of five to six months follow-up
|
Adverse effect-postoperative bleeding
Time Frame: At the end of five to six months follow-up
|
Frequency of postoperative bleeding in the surgical groups
|
At the end of five to six months follow-up
|
Adverse effect - postoperative pain
Time Frame: At the end of five to six months follow-up
|
Frequency of postoperative pain in the surgical groups
|
At the end of five to six months follow-up
|
Adverse effect - postoperative infection
Time Frame: At the end of five to six months follow-up
|
Frequency of postoperative infections in the surgical groups
|
At the end of five to six months follow-up
|
Adverse effect - dental injury
Time Frame: At the end of five to six months follow-up
|
Frequency of dental injury in the surgical groups
|
At the end of five to six months follow-up
|
Adverse effect -anesthetic complication
Time Frame: At the end of five to six months follow-up
|
Frequency of anesthetic complication in the surgical groups
|
At the end of five to six months follow-up
|
Adverse effect - tightness/globus
Time Frame: At the end of five to six months follow-up
|
Difference in proportions having feeling of tightness/globus in throat between the groups
|
At the end of five to six months follow-up
|
Adverse effect - voice problems
Time Frame: At the end of five to six months follow-up
|
Difference in proportions having voice problems between the groups
|
At the end of five to six months follow-up
|
Adverse effect - jaw problems
Time Frame: At the end of five to six months follow-up
|
Difference in proportions having mandibular joint problems between the groups
|
At the end of five to six months follow-up
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Olli-Pekka Alho, MD, PhD, Oulu University Hospital, University of Oulu
- Study Chair: Aleksi EJ Laajala, MD, Oulu University Hospital, University of Oulu
- Study Chair: Paulus Tokola, MD, Oulu University Hospital, University of Oulu
- Study Chair: Timo J Autio, MD, PhD, Oulu University Hospital
- Study Chair: Timo J Koskenkorva, MD, PhD, University of Oulu
- Study Chair: Pasi Ohtonen, M. Sc., Division of Operative Care, Oulu University Hospital, Finland
- Study Chair: Esa Läärä, PhD., Oulu University
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Diary number 113/2020
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Study protocol that includes the Informed Consent Form will be sent to a journal for publication, Statistical analysis Plan will be published later in ClinicalTrials.gov web site.
The data generated or analyzed during this study will be available from the corresponding investigator on reasonable request.
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Tonsillitis Chronic
-
Turku University HospitalRecruitingTonsillitis | Tonsillitis Chronic | Tonsil Disease | Tonsillitis AcuteFinland
-
Hillel Yaffe Medical CenterUnknownChronic Tonsillitis
-
University of BirminghamGlaxoSmithKlineCompletedChronic TonsillitisUnited Kingdom
-
Gaziosmanpasa Research and Education HospitalUnknownTonsillectomy | Tonsillar Hypertrophy | Chronic TonsillitisTurkey
-
Aarhus University HospitalSkodstrup Medical Clinic, DenmarkUnknownStreptococcal Acute TonsillitisDenmark
-
Baylor College of MedicineRecruitingHemorrhage | Otorhinolaryngologic Diseases | Postoperative Pain | Surgery--Complications | Postoperative Hemorrhage | Tonsillectomy | Tonsillitis ChronicUnited States
-
Yonsei UniversityCompletedFollicular Tonsillitis (Chronic)Korea, Republic of
-
Medical University of ViennaCompletedHemorrhage | Otorhinolaryngologic Diseases | Postoperative Pain | Surgery--Complications | Postoperative Hemorrhage | Tonsillectomy | Tonsillitis Chronic | HandlingAustria
-
Fundació Institut de Recerca de l'Hospital de la...CompletedChronic Obstructive Pulmonary Disease | Pharyngitis | Rhinosinusitis | Acute Tonsillitis | Acute BronchitisSpain
-
Georgetown UniversityUnknownSleep Disordered Breathing | Chronic TonsillitisUnited States
Clinical Trials on Tonsillectomy
-
Chinese University of Hong KongRecruitingObstructive Sleep Apnea of ChildHong Kong
-
Kaiser PermanenteWithdrawnObstructive Sleep Apnea | Tonsillitis | Adenotonsillar Hypertrophy
-
Centre Francois BaclesseRecruitingCancer of Head and Neck | AdenopathyFrance
-
Marco Aurelio FornazieriUniversidade Estadual de LondrinaUnknown
-
Karolinska University HospitalTerminated
-
Turku University HospitalRecruitingSleep Apnea, Obstructive | Tonsillar HypertrophyFinland
-
University of ChicagoCompletedObstructive Sleep Apnea SyndromeUnited States
-
University of Southern CaliforniaHenry Ford Health SystemWithdrawnObstructive Sleep ApneaUnited States
-
Chulalongkorn UniversityUnknownObstructive Sleep Apnea | TonsillitisThailand
-
University of CalgaryArthroCare Corporation; Calgary Health RegionUnknownObstructive Sleep ApneaCanada