Sore Throat in Primary Care - a Comparison of Phenoxymethylpenicillin and no Antibiotic Treatment

A Randomized Controlled Clinical Trial of Streptococcus Group A-negative Acute Tonsillitis in Primary Health Care - a Comparison of Phenoxymethylpenicillin and no Antibiotic Treatment

Sore throat is the second most common cause of antibiotic prescribing in primary care in Sweden. Guidelines for sore throat focus on identifying people with sore throat where there are 3 and 4 specified criteria and where near patient tests identify group A streptococci (GAS). In these cases, phenoxymethylpenicillin is recommended.

Studies that have identified microorganisms in sore throat show that there are other bacteria and viruses than GAS, that give similar symptoms and that sometimes no microorganism is trapped despite pronounced symptoms. In recent years, a bacterium F. necrophorum has been identified, which is found in increased incidence of sore throat, but it is also found in healthy individuals. In clinical practice, many patients are treated with penicillin even if GAS is not captured. This may be because the doctor perceives the patient as sick or because other bacteria are not caught with a near patient test which causes the doctor to treat anyway.

The specific aims are to in patients with GAS-negative sore throat and 3 and 4 criteria, aged 15 years and older in primary care, study whether phenoxymethylpenicillin treatment shortens the duration of the disease, reduces the symptom intensity and sickness absence, and investigates the importance of other microorganisms than GAS in sore throat.

The study is a randomized controlled trial in which patients with sore throat are randomized to phenoxymethylpenicillin 3 times daily for 10 days or to no antibiotic therapy. There will also be and a reference group with severe (Centor score 3-4), GAS-positive acute tonsillitis.

Blood samples for inflammatory and immunological response to infections are taken. Throat samples for culture of F. necrophorum and streptococcal groups C and G, as well as polymerase chain reaction (PCR) analysis for bacteria and viruses are also taken at inclusion and at follow-up.

The outcome will be followed in a patient diary for 10 days and at a return visit after 18-24 days where the clinical outcome is asked for and where the blood- and throat samples are repeated.

Follow-up will also takes place via e-mail after 1 and 3 months.

Study Overview

• Status: Unknown
• Conditions: Tonsillitis; Sore Throat
• Intervention / Treatment: Drug: Phenoxymethylpenicillin; Other: No antibiotic treatment

• Study Type: Interventional
• Enrollment (Anticipated): 260
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Katarina Hedin, Ass Prof; Phone Number: +46761369019; Email: katarina.hedin@rjl.se

Study Locations

• Sweden
  • Jönköping, Sweden, 551 85
    • Recruiting
    • Vårdcentralen Rosenhälsan
    • Contact: David Tell, MD
  • Linköping, Sweden, 586 62
    • Recruiting
    • Vårdcentralen Kärna
    • Contact: Anna Moberg, MD
  • Malmö, Sweden, 217 51
    • Recruiting
    • Vårdcentralen Lundbergsgatan
    • Contact: Mia Tyrstrup, MD,PhD
  • Umeå, Sweden, 906 51
    • Not yet recruiting
    • Mariehems hälsocentral
    • Contact: Kia Ericsson, MD
  • Umeå, Sweden, 907 36
    • Not yet recruiting
    • Ålidhems Hälsocentral
    • Contact: Helena Lönneborg, MD
  • Växjö, Sweden, 352 36
    • Recruiting
    • Vårdcentralen Skärvet
    • Contact: Jon Pallon, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

' Centor score 3-4: absence of cough, anamnestic fever (temperature >38.5°C), tender cervical lymphadenitis, and tonsillar exudates (one or both tonsils)

• Duration of symptoms < 8 days
• Rapid antigen detection test for GAS taken and negative
• Willing and able to give informed consent. Subjects under 18 years of age must in addition have the consent from both parents/caretakers

Exclusion Criteria:

• Ongoing antibiotic treatment
• Known or suspected allergies to phenoxymethylpenicillin
• Suspicion of peritonsillar abscess or indication for admittance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Phenoxymethylpenicillin group; Patients randomized to oral phenoxymethylpenicillin 1000 mg three times daily for ten days	Drug: Phenoxymethylpenicillin; tablet PcV 1000 mg x 3 for 10 days; Other Names: Penicillin V (PcV)
Experimental: No antibiotic treatment group; Patients randomized to no antibiotic treatment	Other: No antibiotic treatment; No prescription of antibiotics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in number of days from inclusion to resolution of symptoms	Differences between the randomized groups. Symptom resolution is defined as the first day the item sore throat and difficulty swallowing is scored less than moderately bad	10 days after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportions of patients with symptom resolution at each of the days 2 through 10.		up to 10 days after inclusion
The number of days from inclusion to symptom resolution of the individual items of sore throat symptoms.		10 days after inclusion
Differences in number of days from inclusion to the day the patient can put up with the pain.		up to 10 days after inclusion
The possible change in the self-reported items of symptoms on the rating scale for each of the days 2 through 10 and describe the break through day for improvement	The rating is on a 7-point Likert scale 0=no symptoms, 1= very little, 2=slight, 3=moderately bad, 4=bad, 5=very bad, 6=as bad as it could be.	up to between 10 days after inclusion
The number of days the patient needs to stay at home from work/school		10 days after inclusion
Proportion of patients with future episodes of sore throat		30 days and 3 months after inclusion
Proportion of patients at follow up with eradication of each of the potential pathogens found.	Bacteriological eradication	between 18 up to 24 days
The number of adverse events		3 months after inclusion
Description of patient characteristics and outcomes in the drop-out group.		3 months

Collaborators and Investigators

• Sponsor: Katarina Hedin
• Collaborators: Lund University; Umeå University; Linkoeping University
• Investigators: Principal Investigator: Katarina Hedin, Ass Prof, Region Jonkoping County

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2019
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: September 5, 2019
• First Submitted That Met QC Criteria: September 5, 2019
• First Posted (Actual): September 10, 2019

Study Record Updates

• Last Update Posted (Actual): March 11, 2020
• Last Update Submitted That Met QC Criteria: March 10, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: randomized controlled trial; primary care; sore throat; tonsillitis; phenoxymethylpenicillin
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Tonsillitis; Pharyngitis; Anti-Infective Agents; Anti-Bacterial Agents; Penicillins; Penicillin V
• Other Study ID Numbers: 2019-000756-34

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No