Safety of Discontinuing Patient Antibiotic Treatment

NCT ID: NCT02900820

Last Updated: 2021-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 430 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2020-12-31

Brief Summary

There is no evidence that discontinuing antibiotic therapy for non-bacterial infections is safe. The main objective of this study is to determine whether discontinuation of antibiotic therapy when a clinician no longer considers it necessary makes any difference in terms of the number of days with severe symptoms. This is a multicentre, open-label, randomised controlled clinical trial. The study will be conducted in ten primary care centres in Spain. We will include patients from 18 to 75 years of age with uncomplicated acute respiratory tract infections (RTIs) in whom: antibiotics are not necessary; or those diagnosed with clinical conditions for which antibiotics might be necessary but according to the history and clinical examination the physician considers that antibiotics are not needed or the patient feels that the antibiotic regimen has not worked as expected; or several doses of an antibiotic have been taken from leftovers found in the household or obtained at the pharmacy without any medical prescription for a clinical condition for which antibiotics are not necessary. The patients will be randomly assigned to the usual strategy of continuing antibiotic treatment (usual intervention group) or discontinuing antibiotic therapy (novel intervention group). A sample size of 215 patients per group was calculated on the basis of a reduction of one day in the duration of severe symptoms as a clinically relevant outcome. The primary outcome will be duration of severe symptoms, i.e. symptoms scored 5 or 6 by means of a symptom diary. Secondary outcomes will include: antibiotics taken, adverse events, patient satisfaction, and complications within the first 3 months.

Detailed Description

Introduction: General practitioners (GP) have always been told to continue an antibiotic regimen once the patient has initiated it in order to prevent the patient from acquiring resistant microorganisms. This might be true for confirmed bacterial infections; however, continuing an antibiotic regimen when this is not indicated might hasten the acquisition of resistant organisms and cause adverse events. Since 2011 the Spanish Society of Family Medicine has been recommending GPs to ask their patients to stop taking antibiotics when they suspect a viral infection. However, there is no evidence that discontinuing antibiotic therapy for these conditions is safe. The main objective of this study is to determine whether discontinuation of antibiotic therapy when a GP no longer considers it necessary makes any difference in terms of the number of days with severe symptoms.

Methods: This is a multicentre, open-label, randomised controlled clinical trial. The study will be conducted in ten primary care centres in Spain. We will include patients from 18 to 75 years of age with uncomplicated acute respiratory tract infections (RTIs) in whom: 1. Antibiotics are not necessary; or 2. Those diagnosed with clinical conditions for which antibiotics might be necessary but according to the history and clinical examination the GP considers that antibiotics are not needed or the patient feels that the antibiotic regimen has not worked as expected; or 3. Several doses of an antibiotic have been taken from leftovers found in the household or obtained at the pharmacy without any medical prescription for a clinical condition for which antibiotics are not necessary. The patients will be randomly assigned to the usual strategy of continuing antibiotic treatment (usual intervention group) or discontinuing antibiotic therapy (novel intervention group). A sample size of 215 patients per group was calculated on the basis of a reduction of one day in the duration of severe symptoms as a clinically relevant outcome. The primary outcome will be duration of severe symptoms, i.e. symptoms scored 5 or 6 by means of a symptom diary. Secondary outcomes will include: antibiotics taken, adverse events, patient satisfaction, and complications within the first 3 months. A post-trial implementation observational clinical study by means of a qualitative analysis is planned to be carried out after the clinical trial to know the percentage of the use of the strategy of discontinuing antibiotic treatment and the pros and cons of its use.

Ethics and dissemination: The study was approved by the Ethical Board of Fundació Jordi Gol i Gurina (reference number: 16/093) and informed consent will be obtained from all the patients included. The findings of this trial will be disseminated through research conferences and peer-reviewed journals.

Conditions

Infectious Diseases; Respiratory Tract Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Novel intervention group

Discontinuing antibiotic therapy.

Group Type: EXPERIMENTAL

Discontinuing antibiotic therapy

Intervention Type: OTHER

Patients assigned to this group will be asked to discontinue antibiotic therapy.

Usual intervention group

Usual strategy of continuing antibiotic treatment.

Group Type: EXPERIMENTAL

Continuing antibiotic therapy

Intervention Type: OTHER

Patients assigned to this group will be asked to complete antibiotic therapy.

Interventions

Discontinuing antibiotic therapy

Patients assigned to this group will be asked to discontinue antibiotic therapy.

Intervention Type: OTHER

Continuing antibiotic therapy

Patients assigned to this group will be asked to complete antibiotic therapy.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients diagnosed with clinical conditions for which antibiotics are not necessary;
• Patients diagnosed with a clinical condition for which antibiotics might be necessary but according to the history and clinical examination the primary health physician considers that antibiotics are not needed to be taken or the patients feel that the antibiotic regimen has not worked as expected and feel they need clinical reassessment
• Patients who have taken some doses of an antibiotic (from leftovers found in the household or obtained at the pharmacy without any medical prescription) for a clinical condition for which antibiotics are not necessary

Exclusion Criteria

• Subjects under 18 and over 75 years of age
• Patients with confirmed bacterial infection
• Patients requiring hospital admission
• Severe impairment of signs (impairment of consciousness, respiratory rate > 30 respirations per minute, heart rate > 125 beats per minute, systolic blood pressure < 90 mm Hg, diastolic blood pressure < 60 mm Hg, temperature > 40°C, oxygen saturation < 92%)
• Problems to comply with treatment at home - sociopathy or psychiatric problems, drug or alcohol addiction, or within an inadequate family setting -
• Lack of tolerance to oral treatment, such as the presence of nausea and vomiting, gastrectomy, post-surgery and/or diarrhoea
• Significant comorbidity, including severe renal failure, hepatic cirrhosis, severe heart failure, immunosuppression - chronic HIV infection, transplantation, neutropenic, or patients receiving immunosuppressive drugs or corticosteroids -
• Terminal disease
• Admitted to a long-term residence
• Difficulty to attend the programmed visits
• Refusal to participate in the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spanish Society of Family and Community Medicine

OTHER

Sponsor Role: lead

Responsible Party

Carl Llor

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Josep M Cots, Professor

Role: STUDY_DIRECTOR

University of Barcelona

Locations

Coll d'en Rabassa Primary Health Center

Palma de Mallorca, Balearic Islands, Spain

Manso - Via Roma Primary Care Center

Barcelona, Catalonia, Spain

La Marina Primary Care Center

Barcelona, Catalonia, Spain

Guinardó Primary Care Center

Barcelona, Catalonia, Spain

Jaume I Primary Care Center

Tarragona, Catalonia, Spain

Countries

Spain

References

Gilbert GL. Knowing when to stop antibiotic therapy. Med J Aust. 2015 Feb 16;202(3):121-2. doi: 10.5694/mja14.01201. No abstract available.

Reference Type: BACKGROUND

PMID: 25669463 (View on PubMed)

Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ. 2010 May 18;340:c2096. doi: 10.1136/bmj.c2096.

Reference Type: BACKGROUND

PMID: 20483949 (View on PubMed)

Dekker AR, Verheij TJ, van der Velden AW. Inappropriate antibiotic prescription for respiratory tract indications: most prominent in adult patients. Fam Pract. 2015 Aug;32(4):401-7. doi: 10.1093/fampra/cmv019. Epub 2015 Apr 24.

Reference Type: BACKGROUND

PMID: 25911505 (View on PubMed)

Morgan DJ, Okeke IN, Laxminarayan R, Perencevich EN, Weisenberg S. Non-prescription antimicrobial use worldwide: a systematic review. Lancet Infect Dis. 2011 Sep;11(9):692-701. doi: 10.1016/S1473-3099(11)70054-8. Epub 2011 Jun 12.

Reference Type: BACKGROUND

PMID: 21659004 (View on PubMed)

Goossens H, Ferech M, Vander Stichele R, Elseviers M; ESAC Project Group. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet. 2005 Feb 12-18;365(9459):579-87. doi: 10.1016/S0140-6736(05)17907-0.

Reference Type: BACKGROUND

PMID: 15708101 (View on PubMed)

Llor C, Moragas A, Bayona C, Cots JM, Hernandez S, Calvino O, Rodriguez M, Miravitlles M. Efficacy and safety of discontinuing antibiotic treatment for uncomplicated respiratory tract infections when deemed unnecessary. A multicentre, randomized clinical trial in primary care. Clin Microbiol Infect. 2022 Feb;28(2):241-247. doi: 10.1016/j.cmi.2021.07.035. Epub 2021 Aug 4.

Reference Type: DERIVED

PMID: 34363942 (View on PubMed)

Llor C, Moragas A, Bayona C, Cots JM, Molero JM, Ribas J, Fothy JF, Gutierrez I, Sanchez C, Ortega J, Arranz J, Botanes J, Robles P. The STOP-AB trial protocol: efficacy and safety of discontinuing patient antibiotic treatment when physicians no longer consider it necessary. BMJ Open. 2017 Jun 6;7(5):e015814. doi: 10.1136/bmjopen-2016-015814.

Reference Type: DERIVED

PMID: 28592581 (View on PubMed)

Other Identifiers

16/101

Identifier Type: -

Identifier Source: org_study_id