Condition category
Infections and Infestations
Date applied
02/07/2018
Date assigned
16/08/2018
Last edited
08/01/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Acute lower respiratory infection is common and despite the lack of evidence of benefit antibiotics are often prescribed. Identifying a safe and effective method of symptom control would likely further reduce antibiotic uptake. Pelargonium, a herbal product extracted from the root of P. sidoides in either liquid or tablet form, has been found to have some benefit in treating cough symptoms. The aim of this study is to determine the feasibility of conducting a full trial of Pelargonium sidoides root extract as an alternative to antibiotics for lower respiratory tract infections in UK primary care.

Who can participate?
Patients aged 18 and over with an acute cough (less than 21 days' duration) associated with a lower respiratory infection, where pneumonia is not suspected

What does the study involve?
Participating GP practices are randomly allocated to give either the liquid or tablet preparation, and within each practice, patients are randomly allocated to take either Pelargonium sidoides root extract EPs ®7630 or a placebo (dummy medicine). The use of a delayed prescription for antibiotics is encouraged, but GPs are also able to offer either an immediate prescription for antibiotics or no prescription. Patients are asked to take the medication three times a day, 30 minutes before meals, until 2-3 days after symptom resolution. Patients are asked to complete a daily symptom diary for up to 28 days. Patients can stop completing the diary 2 days after complete resolution of symptoms. A notes review is undertaken after 28 days to document return visits to the GP with a lower respiratory tract infection.

What are the possible benefits and risks of participating?
It is not known whether participants will have any additional benefit from taking part in this trial. However their participation will help to give important information about how best to treat people with chest infections in the future. It is unlikely but participants may experience mild side effects from taking the trial medication.

Where is the study run from?
1. Abbeywell surgery
2. Chawton Park Surgery
3. Oaks Healthcare – Cowplain Family Practice Site
4. Friarsgate Practice
5. Highcliffe Medical Centre
6. Homewell.Curlew Practice
7. Liphook and Liss Surgery
8. Lordshill Health Centre
9. Mulberry House Surgery
10. Park & St Francis Surgery
11. Salisbury Medical Practice
12. Solent NHS Trust
13. Swan Medical Group
14. Swanage Medical Practice
15. The Adam Practice
16. The Andover Health Centre
17. The Cambridge Practice
18. Three Chequers Medical Practice
19. Vine Medical Group
20. Wareham Surgery

When is the study starting and how long is it expected to run for?
April 2017 to March 2019

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Mrs Catherine Simpson
catherine.simpson@soton.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Catherine Simpson

ORCID ID

Contact details

Southampton Clinical Trials Unit
University of Southampton
Centre for Cancer Immunology
MP131 Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
+44 (0)23 8120 5171
catherine.simpson@soton.ac.uk

Additional identifiers

EudraCT number

2016-004598-42

ClinicalTrials.gov number

Protocol/serial number

35629

Study information

Scientific title

Feasibility study of Pelargonium sidoides root extract, EPs®7630 (Kaloba®), for the treatment of acute cough due to lower respiratory tract infection in adults: a double blind, placebo controlled randomised trial

Acronym

HATRIC

Study hypothesis

Acute lower respiratory infection is common and despite the lack of evidence of benefit antibiotics are often prescribed. Identifying a safe and effective method of symptom control would likely further reduce antibiotic uptake. A Cochrane review suggests pelargonium, a herbal product extracted from the root of P. Sidoides in either liquid or tablet formulation, has some benefit in treating cough symptoms. The objective of this trial is to determine the feasibility of conducting a fully powered trial of Pelargonium sidoides root extract as an alternative to antibiotics for lower respiratory tract infections in UK primary care.

Ethics approval

South Central – Berkshire B, 05/01/2018, ref: 17/SC/0653

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Specialty: Primary Care, Primary sub-specialty: Infectious diseases and microbiology; UKCRC code/ Disease: Infection/ Other viral diseases

Intervention

This is a multicentre, double-blind placebo-controlled feasibility trial of Pelargonium sidoides root extract EPs®7630 (Kaloba®).

The trialists aim to recruit 160 adults, 18 years and over, presenting to their GP with an acute cough (≤21 days' duration) as their main symptom and with symptoms localising to the lower respiratory tract (e.g. sputum, chest pain, dyspnoea, wheeze), for which an infective diagnosis is judged very likely.

Sites will be randomised to one of two groups (tablet or liquid preparation) and within each site, patients will be randomised to active or placebo IMP.
Group 1: Liquid Pelargonium sidoides root extract EPs®7630
Group 2: Liquid placebo
Group 3: Tablets of Pelargonium sidoides root extract EPs®7630
Group 4: Placebo tablets

The use of the delayed prescription strategy for antibiotics will be encouraged but clinicians will be able to offer one of three following antibiotic strategies in addition to the randomised intervention:
1. Immediate antibiotics
2. Delayed antibiotics
3. No antibiotics

Participants will be provided with a course of trial medication and a prescription for antibiotics, if considered necessary by the recruiting clinician. If the recruiting clinician uses the delayed prescription strategy then patients will be asked to delay starting taking the antibiotic for 7 -10 days.

Patients will be asked to take the trial medication 3 times a day, 30 minutes before meals, until 2-3 days after symptom resolution. Participants will be asked to complete daily diary data for up to 28 days after presentation. They can stop completing the diary 2 days after complete resolution of symptoms.

Patients will receive follow up phone calls from the research team at the Southampton Clinical Trials Unit (SCTU) at intervals following randomisation to prompt diary completion and return. Participants will be given a £5 shopping voucher on recruitment and when they have returned a fully completed diary.

A notes review will be undertaken 28 days after randomisation to document return visits to the GP with a LRTI.

Intervention type

Other

Phase

Phase II

Drug names

Primary outcome measure

The objective is to determine the feasibility of conducting a fully powered trial of Pelargonium sidoides root extract as an alternative to antibiotics for lower respiratory tract infections in UK primary care. Feasibility objectives and endpoints used to evaluate are detailed below:
1. Eligibility: Number of patients included in and number excluded, with reasons, from the trial from on-site screening logs
2. Recruitment: Ability to recruit patients into the intervention from those attending primary care settings from on-site enrolment records – monthly rate/site adjusted for site list size
3. Randomisation: Willingness to be randomised from the proportion of eligible patients recruited
4. Retention: Across the duration of the intervention and return of a fully completed diary from quantitative data from enrolment, withdrawal rate from study and completion of outcome measures
5. Intervention compliance from diary data and returned medication
6. Patient preference for liquid/tablet formulation from diary data, returned medication and recruitment data
7. Acceptability of the patient diaries, patients’ willingness to complete them and the importance of telephone/text contact from quantitative data collection - percentage of patients returning completed diaries
8. Success of delayed antibiotic strategy from diary data on day antibiotics commenced
9. Need for stratification by antibiotic strategy in main study from proportion allocated to immediate and delayed antibiotic strategy
10. To inform sample size for future trials from rate of outcome measures in the control group.
11. To identify the key resource items to be collected and how often to collect EQ-5D-5L questionnaires in the main trial from data collected in patient diaries and case note reviews

Secondary outcome measures

There are no secondary outcome measures

Overall trial start date

01/04/2017

Overall trial end date

30/07/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Adults 18 years and over
2. Presenting with an acute cough (≤21 days' duration) as their main symptom
3. Presenting with symptoms localising to the lower tract (e.g. sputum, chest pain, dyspnoea, wheeze), for which an infective diagnosis is judged very likely
4. Willing and able to give written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 160; UK Sample Size: 160

Participant exclusion criteria

1. Suspected pneumonia (i.e., complicated lower-respiratory-tract infection) on the basis of focal chest signs (focal crepitations, bronchial breathing) and systemic features (severe breathlessness, high fever, vomiting, severe diarrhoea)
2. Signs of severity which may warrant hospital admission (e.g. SpO2 < 91%, Systolic BP < 90mmHg, Heart rate > 130)
3. Exacerbation of COPD
4. Serious chronic disorders where immediate antibiotics are needed (e.g. cystic fibrosis, valvular heart disease)
5. Unable to give informed consent or complete trial paperwork (including the patient diary)
6. Difficulty reading and understanding English and therefore unable to give informed consent or complete the trial paperwork (including the patient diary)
7. Known or suspected pregnancy
8. Women at risk of pregnancy (i.e. not on effective contraception – combined oral contraceptive pill, an intrauterine hormonal device or subcutaneous hormonal implant)
9. Currently breastfeeding
10. Known immunodeficiency state or chemotherapy
11. Currently taking oral steroids
12. Using a Pelargonium sidoides / Kaloba® preparation and unwilling or unable to discontinue for the study period.
13. Hypersensitivity to pelargonium sidoides preparations or to the Kaloba brand
14. Increased tendency to bleeding or is taking coagulation-inhibiting drugs (e.g. warfarin)
15. Severe hepatic and renal diseases (Chronic Kidney Disease Stage 4, GFR < 30), as no adequate data are available in these areas
16. Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption (tablet formulation only)
17. Previously entered the HATRIC trial
18. Recruited to another interventional trial in the previous 6 weeks

Recruitment start date

14/03/2018

Recruitment end date

21/12/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Abbeywell surgery
Nightingale site Great well drive
Romsey
SO51 7QN
United Kingdom

Trial participating centre

Chawton Park Surgery
Chawton Park Road
Alton
GU34 1RJ
United Kingdom

Trial participating centre

Oaks Healthcare – Cowplain Family Practice Site
26-30 London Road
Cowplain
PO8 8LD
United Kingdom

Trial participating centre

Friarsgate Practice
Stockbridge Road
Winchester
SO22 6EL
United Kingdom

Trial participating centre

Highcliffe Medical Centre
248 Lymington Road Highcliffe
Christchurch
BH23 5ET
United Kingdom

Trial participating centre

Homewell.Curlew Practice
Havant Health Centre Civic Centre Road
Havant
PO9 2AQ
United Kingdom

Trial participating centre

Liphook and Liss Surgery
Station Road
Liphook
GU30 7DR
United Kingdom

Trial participating centre

Lordshill Health Centre
Lordshill District Centre
Southampton
SO16 8HY
United Kingdom

Trial participating centre

Mulberry House Surgery
7 St Denys Road
Southampton
SO17 2GN
United Kingdom

Trial participating centre

Park & St Francis Surgery
Pilgrims Close
Chandlers Ford
SO53 4ST
United Kingdom

Trial participating centre

Salisbury Medical Practice
Fisherton House Fountain Way Wilton Road
Salisbury
SP2 7FD
United Kingdom

Trial participating centre

Solent NHS Trust
Clinical Research Office Room FW. B. 3178. A Royal South Hants Hospital Britons Terrace
Southampton
SO14 0YG
United Kingdom

Trial participating centre

Swan Medical Group
Swan Street
Petersfield
GU32 3AB
United Kingdom

Trial participating centre

Swanage Medical Practice
Station Approach
Swanage
BH19 1HB
United Kingdom

Trial participating centre

The Adam Practice
Upton Health Centre Blandford Road North Upton
Poole
BH16 5PW
United Kingdom

Trial participating centre

The Andover Health Centre
Charlton Road
Andover
SP10 3LD
United Kingdom

Trial participating centre

The Cambridge Practice
276 Lower Farnham Road
Aldershot
GU11 3RB
United Kingdom

Trial participating centre

Three Chequers Medical Practice
Three Swans Surgery Rollestone St
Salisbury
SP1 1DX
United Kingdom

Trial participating centre

Vine Medical Group
Waterlooville Health Centre Dryden close
Waterlooville
PO7 6AJ
United Kingdom

Trial participating centre

Wareham Surgery
Streche Road
Wareham
BH20 4PG
United Kingdom

Sponsor information

Organisation

University of Southampton

Sponsor details

Research and Innovation Services
Room 4079
Building 37
Highfield
Southampton
SO17 1BJ
United Kingdom
+44 (0)23 8059 5058
rgoinfo@soton.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR School for Primary Care Research; Grant Codes: 336

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The protocol will be available once published. Planned publication of the results in a high-impact peer reviewed journal.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

30/07/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

08/01/2019: The following changes have been made: 1. The recruitment end date has been updated from 31/12/2018 to 21/12/2018. 2. The overall trial end date has been updated from 31/03/2019 to 30/07/2019. 3. The intention to publish date has been updated from 31/03/2020 to 30/07/2020.