Tonsillectomy versus watchful waiting in recurrent streptococcal pharyngitis in adults: randomised controlled trial

Participants

From October 2001 to May 2005, consecutive patients referred for tonsillectomy because of recurrent episodes of streptococcal pharyngitis were screened for enrolment at an ear, nose, and throat department of a university hospital. All patients provided written informed consent.

The clinical criterion for study entry was three or more episodes of pharyngitis in six months or four episodes in 12 months. The symptoms and signs during the episodes had to be typical of streptococcal pharyngitis.1 In addition, these episodes had to be severe enough for the patient to seek medical attention and at least one episode had to be group A streptococcal infection proved by culture or rapid antigen test. Exclusion criteria were age under 15 years, history of peritonsillar abscess, ongoing antibiotic treatment for other illness, recurrence probably caused by non-compliance with treatment, major heart or airway disorder or bleeding diatheses that would make same day surgery unfeasible,6 and residence outside the city of Oulu or the neighbouring eight communities.

Study design

We allocated patients to tonsillectomy or the waiting list (control). To avoid disparity between group sizes, we used replacement randomisation. If the disparity exceeded the preset criterion of six, we generated another randomisation list using simple randomisation until we achieved a balanced group size.7 A research assistant not involved in the assignment or care of the trial patients generated the randomisation sequence with a computer random number generator. The assistant concealed the allocation sequence from the investigators who enrolled the participants by putting the assigned treatments in sequentially numbered, opaque, sealed envelopes. These were opened sequentially only after an eligible participant had been found and informed consent obtained, after which a study nurse attached a self fastening slip of paper containing the patient's name to the official study logbook. A trial physician recorded the baseline data and status.

Outcomes

We tested the hypothesis that tonsillectomy in adults with recurrent streptococcal pharyngitis would reduce the short term risk of developing an episode of streptococcal pharyngitis, reduce the rate of all episodes and days with symptoms, and not cause excessive adverse effects.

The primary end point was the proportion of patients with an acute episode of group A streptococcal pharyngitis during the 90 days' follow-up, as determined by signs and symptoms of acute pharyngitis with a positive result of throat culture. The secondary end points were the percentage change in the proportions of patients with all episodes of pharyngitis at 90 days, the times to episodes, and the difference in the mean rates of episodes and days with symptoms during the whole follow-up. Patients recorded episodes and days with symptoms in diaries. We considered an episode to be at least two consecutive days with a sore throat. We recorded data on adverse effects related to tonsillectomy from the diaries and the patients' charts.

Intervention

After baseline data collection and randomisation, the participants were operated on as soon as possible (tonsillectomy group) or placed on the waiting list for tonsillectomy (control group). In the tonsillectomy group, the median time between the randomisation and the tonsillectomy was 13 days (interquartile range 8-21) for practical reasons. The operation was performed under general anaesthesia as day surgery. Four experienced ear, nose, and throat surgeons performed total extracapsular tonsillectomy using blunt or diathermy dissection. In the control group, the waiting times ranged from three to six months, during which time the patients did not receive any prophylactic treatment for their tonsillitis.

Surveillance protocol

We obtained background data and examined the patients at assignment. Both groups were followed up for at least 90 days after randomisation, but otherwise the time of the follow-up visit depended on the length of the waiting list for tonsillectomy in the control group (range 90-210 days) and was 150-180 days in the tonsillectomy group. At randomisation patients in the control group were given the first available date for the operation, the length of follow-up therefore being unrelated to the severity of symptoms.

The primary outcome was objective and based on the presence of group A β haemolytic streptococci in the throat culture during acute pharyngeal symptoms. Patients were given a prepaid microbiological postal package and the phone number of the study nurse with instructions to order a new package immediately after using one. The package included equipment for taking a specimen (Transpocult, Orion Diagnostica, Helsinki, Finland). All participants were advised to visit their own general practitioner whenever they had acute symptoms suggestive of pharyngitis. The general practitioner would then take a culture sample from the pharynx and send it to Oulu University Hospital for analysis. The patients were given written instructions for their general practitioner about the study and illustrated information on how to obtain the culture sample—namely, from the surface of both tonsils or tonsillar fossae in the patients who had undergone tonsillectomy and the posterior pharyngeal wall.3 The patients were told that it was important to seek medical advice for their symptoms during the trial in exactly the same way they had done before the trial and that it was possible to have streptococcal pharyngitis after tonsillectomy.

We plated the swab on sheep blood agar, selecting the growth of streptococci, and incubated them at 35°C for 18-24 hours before reading. The plates were examined again at 48 hours. We used latex agglutination tests (streptococcal grouping kit, Oxoid, Unipath, Hampshire) to differentiate group A streptococcus from the other β haemolytic streptococci. To identify streptococcal carriers, we obtained throat cultures at assignment when the patients were asymptomatic. We were able to serotype streptococcal isolates in case a carrier had a culture positive acute episode. All microbiological analyses were done blinded.

The secondary outcomes were based on the patients' symptoms. Patients used diaries to record their acute symptoms (fever, throat pain, cough, and rhinitis), episodes of pharyngitis, and visits to a doctor. Individuals with acute pharyngitis and positive throat cultures received treatment as prescribed by their own general practitioner. Patients in the tonsillectomy group also documented the duration of postoperative throat pain. At the follow-up visit, we collected the diaries and checked them for completeness.

Statistical analysis

We estimated that we needed to enrol 70 patients for the study to have a statistical power of 80% to detect an absolute difference in streptococcal recurrence rates of 25%, given a 90 day recurrence rate of 25% in the control group and 0% in the tonsillectomy group.8 We considered a two sided P value of 0.05 to indicate significance. For the primary and secondary end points, all participants were analysed on an intention to treat basis.

All data analyses were done according to a pre-established plan. Descriptive data are given as means (SD) or as medians with interquartile ranges. We used the Mann-Whitney U test to compare continuous variables. We constructed survival curves, as they related to the treatment group, according to the Kaplan-Meier method, starting from the date of the randomisation.9 The differences between the groups were tested with the log rank test.10 We calculated the absolute difference and the 95% confidence intervals in the proportions of recurrence between the groups and the respective number needed to treat at 90 days.11 In the tonsillectomy group, we excluded from the risk time the individual recovery times immediately after tonsillectomy during which the patient had continuous throat pain (mean 13 days, SD 4), as reported by patients in their diaries.