Condition category
Respiratory
Date applied
02/12/2008
Date assigned
16/01/2009
Last edited
06/11/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
This study is part of a programme of research into cough/chest infections across 12 European countries. Most people with chest infections probably don’t benefit from antibiotics and inappropriate antibiotic use drives antibiotic resistance, a major global health problem. Some groups of people however might really benefit from antibiotics. The study aims at understanding which subgroups of individuals with chest infections benefit from antibiotics, but also to study antibiotic resistance after antibiotic treatment.

Who can participate?
Throughout Europe 3000 adult patients presenting to primary care with acute cough or other symptoms that suggest a chest infection will take part in this study.

What does the study involve?
If the participating doctors think there is no definite need for antibiotics, participants will be asked to take a 7-day course of tablets to be taken three times a day. The tablets will be either amoxicillin, a very commonly used and safe penicillin-based antibiotic, or a placebo (a tablet without any medication in it). They will not be able to tell whether they will have the real antibiotic or the placebo. Random numbers are used to decide whether participants get antibiotic or placebo to make sure that they have an equal chance of getting either. This is the best way for us to show scientifically whether antibiotics really make a difference. If it is necessary to know whether participants are using an antibiotic or not, the participating doctors will be able to get that information at any time and change the participant’s medication. The participating doctors will also like to take one throat swab at day 8 (extra visit) and at the second study visit (day 28-35). The swab at day 8 will not be taken in all participants. If participants decide they do not want to have a swab taken at day 8 they can still take part in the treatment part of the study.

What are the possible benefits and risks of participating?
The main advantage is that the participating doctors will be well informed about the participants’ illness and will monitor them closely. In the future doctors will be able to provide better management for patients with coughs and chest infections, but this will not benefit the participants during this illness. The main disadvantages are the extra time and discomfort related to taking the additional swabs. The patients who will receive amoxicillin can experience the usual side-effects of penicillin: it can cause mild nausea or diarrhoea, and sometimes it can cause a transient skin rash.

Where is the study run from?
University of Southampton (UK).

When is the study starting and how long is it expected to run for?
October 2007 to April 2010.

Who is funding the study?
EC Sixth Framework Programme.

Who is the main contact?
Prof Paul Little

Trial website

http://www.grace-lrti.org

Contact information

Type

Scientific

Primary contact

Prof Paul Little

ORCID ID

http://orcid.org/0000-0003-3664-1873

Contact details

Primary Medical Care
University of Southampton
Aldermoor Health Centre
Aldermoor Close
Southampton
SO16 5ST
United Kingdom

Type

Scientific

Additional contact

Dr Herman Goossens

ORCID ID

Contact details

Laboratory of Medical Microbiology
Vaccine & Infectious Disease Institute (VAXINFECTIO)
University of Antwerp – Campus Drie Eiken
Universiteitsplein 1
Antwerp
2610
Belgium

Additional identifiers

EudraCT number

2007-001586-15

ClinicalTrials.gov number

Protocol/serial number

GRACE WP10 Protocol v4.1 18/09/2007; GRACE WP10 Protocol v4.2 21/4/2009 (to extend the study with additional networks and a third inclusion period and, only in five networks in the third inclusion period, with an additional objective with associated samples)

Study information

Scientific title

Genomics to combat Resistance against Antibiotics for Community-acquired lower respiratory tract infection (LRTI) in Europe (GRACE) work package 10: Antibiotic Trial One - a randomised placebo-controlled double-blind trial

Acronym

GRACE AT ONE

Study hypothesis

This trial aims at understanding which subgroups of individuals with lower respiratory tract infections (LRTI) benefit from antibiotics. A randomised placebo-controlled double-blind trial will be carried out with patients as unit of randomisation to study the clinical effectiveness of antibiotics in community-acquired LRTI.

More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=4175

Ethics approval

GRACE WP10 Protocol v4.1: Southampton and South West Hampshire REC (B), 31/08/2007, ref: 07/H0504/104
GRACE WP10 Protocol v4.2: amendment approved 21/04/2009
The study protocols were approved by ethics committees in all participating countries. The competent authority in each country also gave their approval.

Study design

Randomised placebo-controlled double-blind trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

GP practices

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Lower respiratory tract infection (LRTI)

Intervention

1. Amoxicillin capsule, gastroenteral use, 3 g a day for 7 days
2. Placebo

Intervention type

Drug

Phase

Phase III

Drug names

Amoxicillin

Primary outcome measures

1. Deterioration of illness: return to doctor with worsening signs, or admission to hospital within 4 weeks of first consultation, measured at one year
2. Symptom severity and duration, duration of symptoms rated moderately bad until symptoms clear, measured by symptom diary (with construct validity), measured at one year

Secondary outcome measures

1. Resource use data, assessed by a review of clinical notes measured at two years
2. Quality of life outcomes for use of economic evaluation (EQ5D), measured at two years

Added 25/11/2014:
3. Antibacterial resistance in oropharyngeal streptococci measured before, immediately after and four weeks after the interventions in five networks in the third inclusion period

Overall trial start date

17/03/2006

Overall trial end date

01/04/2010

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged 18 and over, either sex
2. Acute or worsened cough is the main presentation suggesting LRTI, less than 28 days duration
3. Not been included earlier in the current GRACE trial
4. Able to fill out study materials
5. Immunocompetent
6. Not been on antibiotic treatment in previous month
7. First consultation for this illness episode

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

3000

Participant exclusion criteria

1. Allergic to penicillin
2. History/physical examination suggestive of community acquired pneumonia (CAP)
3. Pregnant

Recruitment start date

15/11/2007

Recruitment end date

14/04/2010

Locations

Countries of recruitment

Belgium, France, Germany, Italy, Netherlands, Poland, Slovakia, Slovenia, Spain, Sweden, United Kingdom

Trial participating centre

University of Southampton
Southampton
SO16 5ST
United Kingdom

Sponsor information

Organisation

University of Southampton (UK)

Sponsor details

Research Governance Office
George Thomas Building 37
Room 4001
Highfield
Southampton
SO17 1BJ
United Kingdom

Sponsor type

University/education

Website

http://www.soton.ac.uk/

Funders

Funder type

Government

Funder name

Sixth Framework Programme

Alternative name(s)

EC Sixth Framework Programme, European Commission Sixth Framework Programme, EU Sixth Framework Programme, European Union Sixth Framework Programme, FP6

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Belgium

Results and Publications

Publication and dissemination plan

We plan to publish on the overall effect of amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected and on a subgroup analysis of potential high-risk groups. Next we plan to publish on the cost-effectiveness of treatment with amoxicillin for acute lower-respiratory-tract infection in primary care and on the selection and persistence of antibiotic resistance in oral streptococci after such treatment.

Participant level data will be stored in a repository, the GRACE Database and Biobank, which is financially supported through the European Science Foundation (ESF), in the framework of the Research Networking Programme TRACE (Translational Research on Antimicrobial resistance and Community-acquired infections in Europe; www.esf.org/trace) and to consult via its chair Herman Goossens.

Intention to publish date

Participant level data

Stored in repository

Results - basic reporting

Publication summary

2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/23265995
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24567620
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25748415
2015 results in: http://erj.ersjournals.com/content/early/2015/11/05/13993003.00611-2015

Publication citations

  1. Results

    Little P, Stuart B, Moore M, Coenen S, Butler CC, Godycki-Cwirko M, Mierzecki A, Chlabicz S, Torres A, Almirall J, Davies M, Schaberg T, Mölstad S, Blasi F, De Sutter A, Kersnik J, Hupkova H, Touboul P, Hood K, Mullee M, O'Reilly G, Brugman C, Goossens H, Verheij T, , Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial., Lancet Infect Dis, 2013, 13, 2, 123-129, doi: 10.1016/S1473-3099(12)70300-6.

  2. Results

    Moore M, Stuart B, COENEN S, Butler CC, Goossens H, Verheij TJ, Little P on behalf of the GRACE consortium, Amoxicillin for acute lower respiratory tract infection in primary care: subgroup analysis of potential high-risk groups, Br J Gen Pract, 2014, 64, 619, e75-e80, doi: 10.3399/bjgp14X677121.

  3. Results

    D Gillespie, K Hood, D Farewell, CC Butler, T Verheij, H Goossens, B Stuart, M Mullee, P Little, Adherence-adjusted estimates of benefits and harms from treatment with amoxicillin for LRTI: secondary analysis of a 12-country randomised placebo-controlled trial using randomisation-based efficacy estimators , BMJ Open, 2015, 5, e006160, doi: 10.1136/bmjopen-2014-006160.

  4. Results

    J Teepe, P Little, N Elshof, B DL Broekhuizen, M Moore, B Stuart, CC Butler, K Hood, M Ieven, S Coenen, H Goossens, TJM Verheij, Amoxicillin for clinically unsuspected pneumonia in primary care: subgroup analysis, Eur Resp J, 2015, doi: 10.1183/13993003.00611-2015.

Additional files

Editorial Notes

On 10/12/2014 the following changes were made to the trial record: 1. The overall trial start date was changed from 01/10/2007 to 17/03/2006. 2. The overall trial end date was changed from 01/04/2010 to 14/04/2010.