The REPOSE (Relative Effectiveness of Pumps Over MDI and Structured Education) trial

ISRCTN	ISRCTN61215213
DOI	https://doi.org/10.1186/ISRCTN61215213
ClinicalTrials.gov (NCT)	NCT01616784
Protocol serial number	HTA 08/107/01
Sponsor	Sheffield Teaching Hospitals NHS Foundation Trust (UK)
Funder	Health Technology Assessment Programme

Submission date: 04/05/2011
Registration date: 11/05/2011
Last edited: 06/09/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
People with Type 1 diabetes (around 250,000 individuals in the UK) cannot produce insulin to control their blood glucose (sugar) and energy needs. They must inject insulin, estimating doses before eating and other activities. This may mean up to 6 injections a day, but aiming for a normal glucose level confers a high risk of hypoglycaemia (low blood glucose, which can cause coma). As a result many patients run glucose levels which are too high and go on to develop complications. Insulin can now be replaced using an infusion pump (the size of a mobile phone), which delivers insulin continuously under the skin via a small plastic tube. This approach is more expensive than multiple injections (£2500 for the pump and £1500 a year extra running costs). It may produce more stable blood glucose, less hypoglycaemia, and a more flexible lifestyle, but needs additional attention from the user. Evidence for benefit comes largely from observing people started on insulin pumps but this may overstate the benefits as those who participate are already committed to the approach or have a particular clinical need. Some of the benefit may come from the re-training and education in insulin use to allow patients to use pumps safely. Importantly, studies of high quality training alone (with standard insulin injections) show similar benefits in blood glucose control, hypoglycaemia and quality of life. No studies in adults have compared pumps with injections where the same training in insulin adjustment has been given, so the added benefit of the pumps themselves is still unclear. There is an urgent need to establish this, and identify patients who benefit the most. The aim of this study is to establish the added benefit of an insulin pump during intensive insulin therapy.

Who can participate?
Patients aged 18 and above with Type 1 diabetes

What does the study involve?
The DAFNE (Dose Adjustment for Normal Eating) course is a 1-week structured course teaching skills in insulin use, delivered in over 70 centres across the UK and Ireland (with over 10,000 individuals now trained). Patients waiting for a DAFNE course are randomly allocated to undertake either the standard DAFNE course with injections, or DAFNE incorporating use of pumps. Blood glucose control, hypoglycaemia, quality of life, acceptability, satisfaction and cost effectiveness are compared between the two groups. We collect information for 2 years after the courses to see if differences develop after some time, or if early improvements are maintained.

What are the possible benefits and risks of participating?
Not provided at time of registration

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

When is the study starting and how long is it expected to run for?
November 2011 to February 2015

Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK)

Who is the main contact?
Prof. Simon Heller
s.heller@sheffield.ac.uk

Contact information

Prof Simon Heller
Scientific

Department of Human Metabolism
University of Sheffield
Room EU38
Beech Hill Road
Sheffield
S10 2RX
United Kingdom

Phone	+44 (0)11 4271 3204
Email	s.heller@sheffield.ac.uk

Study information

Primary study design	Interventional
Study design	Multi-centre parallel-group cluster randomised controlled trial
Secondary study design	Cluster randomised trial
Study type	Participant information sheet
Scientific title	The REPOSE (Relative Effectiveness of Pumps Over MDI and Structured Education): a multi-centre parallel group cluster randomised controlled trial
Study acronym	REPOSE
Study objectives	The aim of the trial is to establish the added benefit of continuous subcutaneous insulin infusion (CSII) therapy over multiple injections on glycaemic control and hypoglycaemia in individuals with type 1 diabetes receiving similar high quality structured training in insulin therapy. The study objectives are as follows: 1. During the randomised controlled trial (RCT) the following measures will be assessed over 2 years: 1.1. Biomedical outcomes (HbA1c, rates of hypoglycaemia, insulin dose, body weight, albumin-creatinine ratio) 1.2. Quantitative and qualitative psychosocial outcomes [quality of life (generic and diabetes specific), treatment satisfaction, fear of hypoglycaemia, hypoglycaemia unawareness, self-efficacy, social support, adherence to treatment, emotional well-being, acceptability of technology] 1.3. Adverse events (severe hypoglycaemia, hospital admissions with hypoglycaemia, diabetic ketoacidosis) 2. Through a combined analysis of the quantitative and qualitative measures we will identify factors which predict and/or help explain outcomes on CSII 3. A cost effectiveness analysis will be undertaken to determine whether the marginal benefits of CSII over optimised multiple daily injection (MDI) (if demonstrated) are commensurate with the marginal costs, as reflected in a cost per quality-adjusted life years (QALY) acceptable to National Institute for Health and Clinical Excellence (NICE)
Ethics approval(s)	NRES Committee North West, 26/04/2011, ref: 11/H1002/10
Health condition(s) or problem(s) studied	Type 1 diabetes
Intervention	The intervention group will be allocated to CSII (Continuous subcutaneous insulin infusion) pump therapy and will attend a 1 week DAFNE (Dose Adjustment for Normal Eating) structured education course followed by a 2 year follow up period during which they will continue to use the CSII treatment. The standard group will be allocated to MDI (multiple daily injection) treatment and will attend a 1 week DAFNE course followed by a 2 year follow up period during which they will continue to use MDI.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Insulin
Primary outcome measure(s)	1. The change in HbA1c after 2 years in those participants whose baseline HbA1c was at or above 7.5% (58mmol/mol) 2. The proportion of participants reaching the NICE target of a HbA1c level of 7.5% (58mmol/mol) or less
Key secondary outcome measure(s)	Biomedical Endpoints: 1. Hypoglycaemia (severe & moderate) 2. Insulin dose 3. Body weight 4. Blood lipids & proteinuria 5. Diabetic ketoacidosis Ancillary Study Endpoints: The ancillary study endpoints will include a prospective psychosocial research component employing mixed methods, quantitative (questionnaires) and qualitative (interviews) approach in order to: 1. Establish whether, and why, there are differences in QoL and other psychological outcomes between patients using CSII and MDI regimens 2. Examine whether, and why, QoL and other outcomes change over time 3. Understand and explore the added benefit (if any) of CSII technology over MDIs from patients and educators perspectives 4. Look at why some patients may do better than others using CSII 5. Explore acceptability of, and reasons for, discontinuing (pump) treatment 6. Enhance understanding, and assist in the interpretation, of trial outcomes (e.g differences in HbA1c between the two arms) Quantitative data will be collected at baseline, 6 months, 1 year and 2 years. Data collected will be Quality of life measures DSQOOL, WHOQOLBREF, SF12 and EQ5D; the Hypoglyceamia Fear Scale (HFS); Diabetes Treatment Satisfaction Questionnaire (DTSQ) and Hospital Anxiety and Depression Scale (HADS). Qualitative data will involve a representative sub-sample of around 40 participants, to include 20 from the CSII arm and 20 from the MDI arm of the trial. These patients will be interviewed within 2 weeks of completion of their courses and around 6 months later. Patients educators will also be invited to take part in an interview and these interviews will also take place within about 2 weeks of the course completion. Health Economic 1. Incremental cost-effectiveness ratio 2. Sensitivity analyses Demographic Measures: Demographics collected will include sex, age, ethnicity, religion and socioeconomic status.
Completion date	28/02/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	280
Key inclusion criteria	1. Aged 18 years and above 2. Have had type 1 diabetes for at least 12 months (as assessed by date clinically diagnosed) 3. Is fluent in speaking, reading and understanding English 4. Has no preference to either CSII or MDI arm of the study and is happy to be randomised 5. Is currently using or willing to switch to insulin detemir 6. Is willing to undertake self monitoring of blood glucose (SMBG), carbohydrate counting and insulin self adjustment (enrolment staff should check that any participant with a baseline HbA1c of above 12% is willing to complete SMBG)
Key exclusion criteria	1. Inability to give informed consent 2. Is pregnant or planning to become pregnant within the next 2 years 3. Has used CSII within the last 3 years 4. Has already completed a diabetes education course 5. Has severe needle phobia 6. Has a current history of alcohol or drug abuse 7. Has a history of heart disease within the past 3 months 8. Has hypertension that is not under control with hypertensive medication (diastolic blood pressure > 100mmHg and or sustained systolic level > 160) 9. Has renal impairment with a chance of needing renal replacement therapy within the next 2 years (enrolment staff should check that creatinine levels are not above 200 µmol/L) 10. Has recurrent episodes of skin infections 11. Has serious or unstable medical or psychological conditions 12. Has taken part in any other investigational clinical trial during the 4 months prior to screening 13. Has any other issue that may preclude the participant from satisfactory participation in the study based on investigatory judgement
Date of first enrolment	01/11/2011
Date of final enrolment	28/02/2015

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

University of Sheffield

Sheffield
S10 2RX
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	07/02/2017		Yes	No
Results article	results	30/03/2017		Yes	No
Results article	results	01/04/2017		Yes	No
Protocol article	protocol	03/09/2014		Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

06/09/2019: ClinicalTrials.gov number added.
26/04/2017: Publication reference added.
03/04/2017: Publication reference added.
09/02/2017: Publication reference added.
18/04/2016: Plain English summary added.