Chronic Otitis Media
Conditions
Brief summary
Chronic suppurative otitis media is one of the most common chronic infections in children worldwide. Symptoms include otorrhea, otalgia and hearing loss. In many countries, it is treated primarily with antibiotics; in other countries such as the Netherlands a surgical approach, such as a tonsillectomy, adenoidectomy, placement or removal of tympanostomy tubes or a tympanomastoidectomy is preferred. There is however, no agreement on the management of this disease. The purpose of this study is to determine the effectiveness of treatment with sulfamethoxazole-trimethoprim for 6-12 weeks in children suffering from chronic otitis media and otorrhea.
Detailed description
Chronic suppurative otitis media is one of the most common chronic infections in children worldwide. Symptoms include otorrhea, otalgia and hearing loss. In many countries it is treated primarily with antibiotics; in other countries such as the Netherlands a surgical approach, such as a tonsillectomy, adenoidectomy, placement or removal of tympanostomy tubes or a tympanomastoidectomy is preferred. There is however, no agreement on the management of this disease. Co-trimoxazole is an inexpensive antibiotic and tolerated well by children, also when long treatment regimens or prophylaxis is necessary. A previously performed retrospective study of 48 children who were referred to the pediatric department of otorhinolaryngology in the UMC Utrecht because of therapeutic resistant otorrhea showed promising results; after 3 months follow-up, 52% of the patients were otorrhea free, 25% had otorrhea incidentally and 23% showed no signs of improvement. Therefore, the treatment of chronic otitis media with sulfamethoxazole-trimethoprim for a minimum of six weeks is promising and might be a good alternative to surgical treatment. The purpose of this study is to determine the effectiveness of treatment with sulfamethoxazole-trimethoprim during 6-12 weeks in children with chronic otitis media and otorrhea for more than 12 weeks.
Interventions
18 mg/kg, two times a day
DRUGPlacebo
Sponsors
Dutch Health Care Insurance Board
UMC Utrecht
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* age between 1 and 12 years * otorrhea for more than 3 months
Exclusion criteria
* cholesteatoma * known immune deficiency other than IgA or IgG2 * Down's syndrome * craniofacial anomalies * cystic fibrosis * immotile cilia syndrome * allergy to sulfamethoxazole-trimethoprim * continuous use of sulfamethoxazole-trimethoprim for more than six weeks in the past six months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Otomicroscopic Signs of Otorrhea in Either Ear | 6, 12 weeks and 1 year follow-up. | The primary endpoint was otomicroscopic signs of otorrhea in either ear in the presence of a tympanostomy tube or tympanic membrane perforation at 6 and 12 weeks and 1 year follow-up. At these follow-up moments the participants were checked for the presence of otorrhea using an otomicroscope. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Used Additional Antibiotic Eardrops Between 6 to 12 Week Follow-up | Between 6 to12 week follow up | Parents kept a diary of study medication and additional medication used for their child's' ear disease, including eardrops. These data were collected at the follow-up visits. |
| Number of Patients Who Used Additional Antibiotic Eardrops Between 12 Weeks to 1 Year Follow-up | between 12 weeks to 1 year follow-up | Parents kept a diary of study medication and additional medication used for their child's' ear disease, including eardrops. These data were collected at the follow-up visits. |
| Number of Patients Who Used Systemic Antibiotics Other Than the Study Medication Between 6 and 12 Weeks Follow-up. | between 6 and 12 weeks follow-up | Parents kept a diary of study medication and additional medication used for their child's' ear disease, including additional use of systemic antibiotics other than the study medication. These data were collected at the follow-up visits. |
| Number of Patients Who Used Systemic Antibiotics Other Than the Study Medication Between 12 Weeks and 1 Year Follow-up. | between 12 weeks and 1 year follow-up | Parents kept a diary of study medication and additional medication used for their child's' ear disease, including additional use of systemic antibiotics other than the study medication. These data were collected at the follow-up visits. |
| Number of Patients Who Underwent Ear Nose and Throat Surgery Between 12 Weeks and 1 Year Follow-up. | between 12 weeks and 1 year follow-up | After 12 weeks follow-up irrespective of the presence or absence of otorrhea the study medication was discontinued. After the first 12 weeks local otorhinolaryngologists and paediatricians were free to manage symptoms of otorrhea according to their regular practice. Parents kept a diary between 12 weeks and 1 year follow-up where Ear Nose and Throat Surgery was noted. This outcome describes the number of patients who underwent Ear Nose and Throat Surgery between 12 weeks and 1 year follow-up. |
Countries
Netherlands
Participant flow
Recruitment details
Patients were recruited between February 2003 and June 2006. Otorhinolaryngologists and paediatricians from all over the Netherlands referred potential participants, i.e. children with COM that had failed conventional management with topical medications and/or short term systemic antibiotics
Participants by arm
| Arm | Count |
|---|---|
| Placebo Children assigned to the placebo group received two times a day a placebo for 6 to 12 weeks. The placebo was a blinded suspension with an identical taste, bottle and fluid appearance as the sulfamethoxazole-trimethoprim suspension. When at the first control visit after 6 weeks otorrhea was found to be present in either ear, the study medication was continued for another 6 weeks. The study medication was discontinued if both ears were found to be free from otorrhea and parents confirmed that they had seen no signs of otorrhea during the previous week. Parents were instructed to start the study medication again if symptoms of otorrhea recurred between the follow-up visits at 6 and 12 weeks. At inclusion and if otorrhea was present at 6 and 12 weeks follow-up, antibiotic with corticosteroid eardrops were prescribed in addition to the study medication for 7 to 10 days. After 12 weeks follow-up the study medication was discontinued irrespective of the presence or absence of otorrhea. | 51 |
| Sulfamethoxazole-trimethoprim Children assigned to the Sulfamethoxazole-trimethoprim group received Sulfamethoxazole-trimethoprim orally (18mg/kg two times a day) for 6 to 12 weeks. When at the first control visit after 6 weeks otorrhea was found to be present in either ear, the study medication was continued for another 6 weeks. The study medication was discontinued if both ears were found to be free from otorrhea and parents confirmed that they had seen no signs of otorrhea during the previous week. Parents were instructed to start the study medication again if symptoms of otorrhea recurred between the follow-up visits at 6 and 12 weeks. At inclusion and if otorrhea was present at 6 and 12 weeks follow-up, antibiotic with corticosteroid eardrops were prescribed in addition to the study medication for 7 to 10 days. After 12 weeks follow-up the study medication was discontinued irrespective of the presence or absence of otorrhea. | 50 |
| Total | 101 |
Baseline characteristics
| Characteristic | Placebo | Sulfamethoxazole-trimethoprim | Total |
|---|---|---|---|
| Age Continuous | 51 months | 48 months | 50 months |
| Sex: Female, Male Female | 25 Participants | 22 Participants | 47 Participants |
| Sex: Female, Male Male | 26 Participants | 28 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 50 | 1 / 51 |
| serious Total, serious adverse events | 1 / 50 | 1 / 51 |
Outcome results
Primary
Number of Participants With Otomicroscopic Signs of Otorrhea in Either Ear
The primary endpoint was otomicroscopic signs of otorrhea in either ear in the presence of a tympanostomy tube or tympanic membrane perforation at 6 and 12 weeks and 1 year follow-up. At these follow-up moments the participants were checked for the presence of otorrhea using an otomicroscope.
Time frame: 6, 12 weeks and 1 year follow-up.
Population: intention to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sulfamethoxazole-trimethoprim | Number of Participants With Otomicroscopic Signs of Otorrhea in Either Ear | At 6 weeks | 13 participants |
| Sulfamethoxazole-trimethoprim | Number of Participants With Otomicroscopic Signs of Otorrhea in Either Ear | At 12 weeks | 15 participants |
| Sulfamethoxazole-trimethoprim | Number of Participants With Otomicroscopic Signs of Otorrhea in Either Ear | At 12 months | 11 participants |
| Placebo | Number of Participants With Otomicroscopic Signs of Otorrhea in Either Ear | At 6 weeks | 27 participants |
| Placebo | Number of Participants With Otomicroscopic Signs of Otorrhea in Either Ear | At 12 weeks | 23 participants |
| Placebo | Number of Participants With Otomicroscopic Signs of Otorrhea in Either Ear | At 12 months | 9 participants |
Comparison: Assuming a spontaneous recovery of 25% and a treatment effect of TMP-SMX of 50% (based on a retrospective study of children treated with TMP-SMX for COM at our hospital), and taking α=0.05 and a power of 0.80, we calculated that each group should consist of 50 children.~Rate differences with 95% confidence intervals were calculated at the three control visits to compare both groups for the outcome measures.95% CI: [-44, -6]risk differences (RD)
Comparison: Assuming a spontaneous recovery of 25% and a treatment effect of TMP-SMX of 50% (based on a retrospective study of children treated with TMP-SMX for COM at our hospital), and taking α=0.05 and a power of 0.80, we calculated that each group should consist of 50 children.~Rate differences with 95% confidence intervals were calculated at the three control visits to compare both groups for the outcome measures.95% CI: [-34, 4]risk difference (RD)
Comparison: Assuming a spontaneous recovery of 25% and a treatment effect of TMP-SMX of 50% (based on a retrospective study of children treated with TMP-SMX for COM at our hospital), and taking α=0.05 and a power of 0.80, we calculated that each group should consist of 50 children.~Rate differences with 95% confidence intervals were calculated at the three control visits to compare both groups for the outcome measures.95% CI: [-12, 22]risk difference (RD)
Secondary
Number of Patients Who Underwent Ear Nose and Throat Surgery Between 12 Weeks and 1 Year Follow-up.
After 12 weeks follow-up irrespective of the presence or absence of otorrhea the study medication was discontinued. After the first 12 weeks local otorhinolaryngologists and paediatricians were free to manage symptoms of otorrhea according to their regular practice. Parents kept a diary between 12 weeks and 1 year follow-up where Ear Nose and Throat Surgery was noted. This outcome describes the number of patients who underwent Ear Nose and Throat Surgery between 12 weeks and 1 year follow-up.
Time frame: between 12 weeks and 1 year follow-up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sulfamethoxazole-trimethoprim | Number of Patients Who Underwent Ear Nose and Throat Surgery Between 12 Weeks and 1 Year Follow-up. | 13 participants |
| Placebo | Number of Patients Who Underwent Ear Nose and Throat Surgery Between 12 Weeks and 1 Year Follow-up. | 11 participants |
95% CI: [-12, 24]Rate differences (95%CI intervals)
Secondary
Number of Patients Who Used Additional Antibiotic Eardrops Between 12 Weeks to 1 Year Follow-up
Parents kept a diary of study medication and additional medication used for their child's' ear disease, including eardrops. These data were collected at the follow-up visits.
Time frame: between 12 weeks to 1 year follow-up
Population: Parents kept a diary of study medication and additional medication used for their child's' ear disease, including eardrops. These data were collected at the follow-up visits. Some parents did not fill in the required forms and these were excluded in this analysis. Therefore number of participants analyzed differ from the flow-chart.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sulfamethoxazole-trimethoprim | Number of Patients Who Used Additional Antibiotic Eardrops Between 12 Weeks to 1 Year Follow-up | 29 participants |
| Placebo | Number of Patients Who Used Additional Antibiotic Eardrops Between 12 Weeks to 1 Year Follow-up | 31 participants |
95% CI: [-22, 14]rate difference (RD)
Secondary
Number of Patients Who Used Additional Antibiotic Eardrops Between 6 to 12 Week Follow-up
Parents kept a diary of study medication and additional medication used for their child's' ear disease, including eardrops. These data were collected at the follow-up visits.
Time frame: Between 6 to12 week follow up
Population: Parents kept a diary of study medication and additional medication used for their child's' ear disease, including eardrops. These data were collected at the follow-up visits. Some parents did not fill in the required forms and these were excluded in this analysis. Therefore number of participants analyzed differ from the flow-chart.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sulfamethoxazole-trimethoprim | Number of Patients Who Used Additional Antibiotic Eardrops Between 6 to 12 Week Follow-up | 21 participants |
| Placebo | Number of Patients Who Used Additional Antibiotic Eardrops Between 6 to 12 Week Follow-up | 26 participants |
95% CI: [-34, 10]rate differences (95%CI intervals)
Secondary
Number of Patients Who Used Systemic Antibiotics Other Than the Study Medication Between 12 Weeks and 1 Year Follow-up.
Parents kept a diary of study medication and additional medication used for their child's' ear disease, including additional use of systemic antibiotics other than the study medication. These data were collected at the follow-up visits.
Time frame: between 12 weeks and 1 year follow-up
Population: Parents kept a diary of study medication and additional medication used for their child's' ear disease, including additional use of systemic antibiotics other than the study medication. These data were collected at the follow-up visits. Some parents did not fill in the required forms and these were excluded in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sulfamethoxazole-trimethoprim | Number of Patients Who Used Systemic Antibiotics Other Than the Study Medication Between 12 Weeks and 1 Year Follow-up. | 23 participants |
| Placebo | Number of Patients Who Used Systemic Antibiotics Other Than the Study Medication Between 12 Weeks and 1 Year Follow-up. | 18 participants |
95% CI: [-7, 37]Rate difference (RD)
Secondary
Number of Patients Who Used Systemic Antibiotics Other Than the Study Medication Between 6 and 12 Weeks Follow-up.
Parents kept a diary of study medication and additional medication used for their child's' ear disease, including additional use of systemic antibiotics other than the study medication. These data were collected at the follow-up visits.
Time frame: between 6 and 12 weeks follow-up
Population: Parents kept a diary of study medication and additional medication used for their child's' ear disease, including additional use of systemic antibiotics other than the study medication. These data were collected at the follow-up visits. Some parents did not fill in the required forms and these were excluded in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sulfamethoxazole-trimethoprim | Number of Patients Who Used Systemic Antibiotics Other Than the Study Medication Between 6 and 12 Weeks Follow-up. | 4 participants |
| Placebo | Number of Patients Who Used Systemic Antibiotics Other Than the Study Medication Between 6 and 12 Weeks Follow-up. | 7 participants |
95% CI: [-23, 9]Rate differences (95%CI interval)