Study of 5 and 10 Days Treatment With Penicillin Against Sore Throat Caused by Streptococci

A Randomized Controlled Study of 5 and 10 Days Treatment With Phenoxymethylpenicillin for Pharyngotonsillitis Caused by Streptococcus Group A

The primary objective of the study is to compare the clinical efficacy of 5 days (800 mg x 4) versus 10 days (1000 mg x 3) treatment with phenoxymethylpenicillin (PcV) in adults, adolescents and children with streptococcal tonsillitis. Patients are recruited from 17 primary Health care centres in the south of Sweden. Adult men and women, youth and children ≥ 6 years of age who are visiting the primary Health care for sore throat with suspected tonsillitis and meeting the criteria in accordance with current treatment recommendations for pharyngotonsillitis, ie 3-4 Centor criteria (fever≥ 38.5, tender lymph nodes, coatings of the tonsils and absence of cough) and a positive rapid antigen detection test (RADT) for Group A streptococcus (GAS) will be included in the study. Patients will be randomized to be prescribed PcV of 5 and 10 days. Each patient or guardian fills daily in a short diary including aches, fever, PcV doses, pain relievers, adverse events etc. Five to seven days after last intake of PcV the general practioner make a clinical judgement if the patient has recovered from the pharyngotonsillitis. Questions to be asked are if remaining symptoms or new symptoms of sore throat is present, if adverse events have been noted or of any extra physician visits have been made. Throat swab for semi quantitative cultures of Streptococcus group A, C and G are made at randomization and five to seven days after last intake of PcV. A study nurse will contact the patients one month and three months after the last treatment day for follow-up. If the patient has reconsulted or been hospitalised for a sore throat or possible complication, those patient records will be examined.

Study Overview

• Status: Completed
• Conditions: Tonsillitis
• Intervention / Treatment: Drug: Phenoxymethylpenicillin

• Study Type: Interventional
• Enrollment (Actual): 433
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Alvesta, Sweden, 342 30
    • Alvesta vårdcentral
  • Bollebygd, Sweden, 517 36
    • Närhälsan Bollebygd Vårdcentral
  • Bunkeflostrand, Sweden, 21840
    • Capio Citykliniken Bunkeflo Hyllie
  • Eslöv, Sweden, 241 31
    • Vårdcentralen Tåbelund
  • Fristad, Sweden, 513 33
    • Närhälsan Fristad vårdcentral
  • Lessebo, Sweden, 360 50
    • Vardcentralen Lessebo
  • Limhamn, Sweden, 216 16
    • Capio Citykliniken Malmö Limhamn
  • Löddeköpinge, Sweden, 24630
    • Löddeköpinge vårdcentral
  • Malmö, Sweden, 214 33
    • Vårdcentralen Sorgenfrimottagningen
  • Malmö, Sweden, 21715
    • Vårdcentralen Lundbergsgatan
  • Sandared, Sweden, 518 32
    • Närhälsan Sandared vårdcentral
  • Sjöbo, Sweden, 27531
    • Vårdcentrlaen Sjöbo
  • Skövde, Sweden, 541 41
    • Närhälsan Billingen vårdcentral
  • Skövde, Sweden, 541 41
    • Närhälsan Norrmalm vårdcentral
  • Skövde, Sweden, 541 64
    • Närhälsan Södra Ryd
  • Växjö, Sweden, 351 85
    • Vårdcentrlaen Strandbjörket
  • Växjö, Sweden, 35261
    • Capio vårdcentralen Hovshaga

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults, adolescents and children ≥ 6 years of age with verified streptococcal pharyngotonsillitis.

Exclusion Criteria:

• Signs of serious infection.
• Known hypersensitivity against penicillin.
• Chronic disease with effect on the immune response.
• Immunosuppressive treatment.
• Streptococcal tonsillitis within one month (relapse).

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
Experimental: 5 days; Phenoxymethylpenicillin 800 mg x 4 for 5 days	Drug: Phenoxymethylpenicillin; Other Names: Penicillin V
Active Comparator: 10 days; Phenoxymethylpenicillin 1000 mg x 3 for 10 days	Drug: Phenoxymethylpenicillin; Other Names: Penicillin V

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical cure	Difference between treatment groups in the rate of clinical cure. Clinical cure is defined as clinical judgement by physician and absence of Centor criteria (coating, fever and swollen Large Granular Lymphocyte glands).	5-7 days after discontinuation of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacteriological cure	Difference between treatment groups in the rate of bacteriological cure, defined as absence of GAS in culture.	5-7 days after discontinuation of treatment
Frequency of relapses		1 month after discontinuation of treatment
Frequency of complications		Within 3 months after discontinuation of treatment

Collaborators and Investigators

• Sponsor: Ass. Prof. Katarina Hedin
• Investigators: Principal Investigator: Sigvard Mölstad, Professor, Lund University; Principal Investigator: Katarina Hedin, MD PhD, Department of Research and Development, Region Kronoberg and Lund University; Principal Investigator: Pär-Daniel Sundvall, MD PhD, Research and Development Unit, Primary Health Care in Southern Älvsborg County and University of Gothenburg

Publications and helpful links

General Publications

• Tell D, Tyrstrup M, Edlund C, Rystedt K, Skoog Stahlgren G, Sundvall PD, Hedin K. Clinical course of pharyngotonsillitis with group A streptococcus treated with different penicillin V strategies, divided in groups of Centor Score 3 and 4: a prospective study in primary care. BMC Infect Dis. 2022 Nov 11;22(1):840. doi: 10.1186/s12879-022-07830-4.
• Skoog Stahlgren G, Tyrstrup M, Edlund C, Giske CG, Molstad S, Norman C, Rystedt K, Sundvall PD, Hedin K. Penicillin V four times daily for five days versus three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci: randomised controlled, open label, non-inferiority study. BMJ. 2019 Oct 4;367:l5337. doi: 10.1136/bmj.l5337.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: March 4, 2016
• First Submitted That Met QC Criteria: March 14, 2016
• First Posted (Estimate): March 18, 2016

Study Record Updates

• Last Update Posted (Actual): November 14, 2018
• Last Update Submitted That Met QC Criteria: November 9, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Pharyngitis; Tonsillitis; Anti-Infective Agents; Anti-Bacterial Agents; Penicillins; Penicillin V
• Other Study ID Numbers: FoHM/Tonsillit2015; 2015-001752-30 (EudraCT Number)

Plan for Individual participant data (IPD)

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