Clinical trial NCT05431296: Glucose Monitoring After Acute Myocardial Infarct in People With Diabetes
Official title: Glucose Monitoring After Acute Myocardial Infarct in People With Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 2 Diabetes
Acute Myocardial Infarction
Acute Myocardial Infarction With ST Elevation
Diabetes Complications
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2022-06-24
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Randomised control trial
Primary purpose: TREATMENT

Brief summary: Glucose monitoring after Acute Myocardial infarct in people with diabetes is a Dexcom funded study that is investigating whether the use of continuous glucose monitors (Dexcom ONE model) in people with type 2 diabetes facilitates time in glycaemic range in the 6 months after an acute myocardial infarction. As an exploratory outcome it will investigate whether time in glycaemic range is associated with changes in mortality and major adverse cardiac events in the 6 months after acute myocardial infarct.

Detailed description: The study

1. Patients recruited from cardiology services after ACS (n=140 participants)

   Following informed consent study participants with known diabetes who have had an acute myocardial infarct will be recruited. Participants will be randomly allocated to either the intervention group, referred to as cohort 'a', or to the control group, referred to cohort 'b'. They will be randomised using permuted blocks in a 5:2 ratio (intervention:control). CGM (real-time or blinded) will be applied to participants prior to discharge.

   Following hospital discharge, the effects of changes in blood glucose levels on cardiac and health outcomes will be evaluated. Participants recruited to cohort 'a' will wear real-time CGM continuously after hospital discharge for 26 weeks. They will have face-to-face, telephone or video reviews of CGM data at 4 and 12 weeks with clinician-led diabetes treatment escalation according to NICE guidelines based aiming for \>70% time in target blood glucose range, 3.9-10mmol/L (50% for older or high risk individuals). Participants recruited to cohort 'b' will wear blinded CGM for 10 days after insertion. They will wear blinded CGM again for 10 days , with the second sensor insertion at days 17-23, third sensor insertion during week 10 and fourth sensor insertion during week 24. Following each sensor wear, participants in cohort 'b' will have a study visit when their sensor data will be downloaded. Participants in cohort 'b' will receive face-to-face or remote support to insert and establish blinded CGM but no clinical review and the participant should manage their diabetes as the participant normally would. At 26 weeks data will be analysed for all primary and secondary outcomes.

   The participants who receive real-time CGM will be compared to age and sex-matched controls, who's data will be obtained from the NIHR Cardiovascular Health Informatics Collaborative for comparison of cardiovascular outcomes.

   At 26 weeks data (clinical details of hospital admissions, further cardiac events, medication changes, blood test results obtained from hospital records and on discussion with the participant) will be collected for all primary and secondary outcomes. Imperial College Healthcare NHS Trust uses an electronic patient record system that is connected to the central NHS Spine and is updated in real-time. People who have died, even if the person has died out of hospital, will be recorded as deceased and this will be visible to the research team. End of study will be defined as Last Subject Last Visit (LSLV) at which point the participant will be asked to return or post back their study equipment and the participant will revert to standard care with their usual GP, community or hospital diabetes team.

   If participants in cohort 'a' wish to continue real time CGM beyond the primary endpoint, they will be given the opportunity to continue to use CGM in an open label observation phase for three years from the start of the study. The study will continue to supply all CGM equipment to participants. The participant's GP, and if appropriate, specialist diabetes team, will be made aware that they are continuing on CGM for research purposes. The CGM data will continue to be collected by the study team for research purposes and the participant will have 6 monthly contact from the study team by telephone, virtually, in person or by email, in line with the participant's preference. The purpose of these visits will be to give CGM supplies, check that the participant still wishes to continue on CGM, and to gather information on diabetes medications, and major adverse cardiac events.

   The study team will not be managing the participant's diabetes over the extension phase and their diabetes care will revert to the team who had previously managed it. During the observational phase, the trial team will not directly make changes to diabetes care on the basis of the results of the additional CGM but results that are significant to the participant's care, or any incidental findings, will be transmitted to their usual care giver and this may result in changes to their diabetes management. It is not anticipated that there will be incidental findings. Participants will be encouraged to contact the study team if they have any problems or concerns in relation to the ongoing use of the sensors.

   Eligible participants admitted to the Hammersmith Hospital HAC with confirmed ACS will be recruited as soon as possible after hospital admission. Patients lacking capacity to consent will not be recruited. During admission, HbA1c levels will be sent as part of routine blood testing.

   The research team will collect full medical and medication history, as well as historic bloods test results from the hospital computer systems as per routine clinical care. All participants recruited during their hospital admission will have blood tests (for HbA1c and other markers of metabolism) during admission and at 4, 12 and 24-26 weeks.

   Participants in cohorts 'a' and 'b' will be asked to complete the Diabetes Treatment Satisfaction Scale questionnaire, the Audit of Diabetes Dependent Quality of Life questionnaire and the Hypoglycaemia Symptom Rating Questionnaire at the time of recruitment, and then at 4, 12, and 24 weeks. Participants will also be asked to fill out an Audit of Diabetes Dependent Quality of Life-19 questionnaire at the time of recruitment and at 12 and 24 weeks.
2. Patients recruited from diabetes and cardiology clinics after ACS (n=20 participants)

   Eligible participants reviewed in clinic with confirmed previous ACS will be recruited. Patients lacking capacity to consent will not be recruited. HbA1c levels will be sent as part of routine blood testing. The research team will collect full medical and medication history, as well as historic bloods test results from the hospital computer systems as per routine clinical care.

   Blinded CGM will be applied to 20 participants with a history of ACS more than 6 months ago, but less than 10 years ago and a known diagnosis of type 2 diabetes who take one or oral diabetic agents, and/or GLP 1 receptor analogue, and/or insulin. The blinded CGM will be worn for 10 days and then returned to (or collected by) the study team.

   These participants be asked to complete a Diabetes Treatment Satisfaction Scale questionnaire, the Audit of Diabetes Dependent Quality of Life questionnaire and the Hypoglycaemia Symptom Rating Questionnaire at the time of recruitment. The participants will have a blood test looking at glycaemic control and markers of metabolism at the time of recruitment.
3. Data collection from the Health Information Collaborative

The participants who receive real-time CGM will be compared to age and sex-matched controls, who's data will be obtained from the NIHR Cardiovascular Health Informatics Collaborative for comparison of cardiovascular outcomes. Imperial College Healthcare NHS Trust has led the NIHR Cardiovascular Health Informatics Collaborative, which was established to enable the sharing and repurposing of routinely captured clinical data for re-use in research. Clinical patient data is extracted and put into a tabular format which includes demographics, emergency department attendance, inpatient episodes, blood tests, diagnoses, operations and procedures, echocardiography measurements and survival status. This infrastructure has been used to investigate patient outcomes in previous studies and will provide endpoint data for the patients enrolled into this study.

2. Clinical study recruitment: Single Centre- Imperial College Healthcare NHS Trust Design: Randomised control trial

Population:

Interventional cohort: 100 participants with type 2 diabetes and acute myocardial infarction will wear real time CGM for 26 weeks Control: 40 participants with type 2 diabetes and acute myocardial infarction will wear blinded CGM for 10 days at 4 time points in the 6 months after infarct.

Clinic cohort: 20 participants with type 2 diabetes who have had a myocardial infarct \> 6 months ago but \<10 years ago will wear blinded CGM for 10 days.

Case control: NIHR Cardiovascular Health Informatics Collaborative dataset

Timescale: Each participant will be in the trial for 6 months. It is anticipated that it will take 18-24 months to recruit to target study number.

3. Statistics The study is powered to detect a change of between 7.2 and 13.2% difference in time in range glucose 3.9-10mmol/l between the real time and blinded CGM groups at 6 months depending the standard deviation used in the power calculation with two tailed alpha of 0.05 and power of 80%. This difference is thought to be a clinically meaningful and achievable difference.

For each questionnaire, mean ± SD values or percentiles appropriate to the distribution will be given by randomization group for the total score and each subscale. Treatment group comparisons will be made using linear models.

The following tabulations will be performed according to treatment group without statistical testing: baseline demographics and clinical characteristics, protocol deviations, device malfunctions and other reported device issue.

For all CGM outcomes, a multilevel model of repeated measures (MMRM) will be used.

4. Data During the course of the study visits some data will be stored on laptop computers, not connected to the Internet, for later statistical analysis. These data will be coded and non- identifiable. Laptop computers may be used during the visits for portability and convenience. At the end of each visit the anonymised data will be transferred immediately to a secure web-server (details below) and will be deleted from the laptop.

Any identifiable participant data will be stored in a locked filing cabinet in a secure room in each investigation centre. Only clinical research team will have access to this participant identifiable data.

5. Adverse Events (AEs) Reporting Procedures. All adverse events will be reported. Depending on the nature of the event the reporting procedures below will be followed. Any questions concerning adverse event reporting will be directed to the Chief Investigator in the first instance.

Non serious AEs: All such events will be recorded. Serious Adverse Events (SAEs): An SAE form will be completed and faxed to the Chief Investigator within 24 hours. However, hospitalisations for elective treatment of a pre-existing condition do not need reporting as SAEs.

Reports of related and unexpected SAEs will be submitted within 15 days of the Chief Investigator becoming aware of the event. The Chief Investigator will also notify the Sponsor of all SAEs, where in the opinion of the Chief Investigator, the event is:

'related', i.e. resulted from the administration of any of the research procedures; and 'unexpected', i.e. an event that is not listed in the protocol as an expected occurrence Local investigators will report any SAEs as required by their Local Research Ethics Committee, Sponsor and/or Research \& Development Office.

Eligibility criteria: Inclusion Criteria:

From the Hammersmith Hospital In-patient Cardiology Services:

* Adults aged \>18 years
* Known or newly diagnosed type 2 diabetes
* Taking one or more oral hypoglycaemic agent, GLP1 receptor analogue and/or insulin
* Admitted to Hammersmith Hospital cardiology inpatient services with ACS
* Raised blood troponin level on admission

From Imperial College Healthcare Trust Diabetes and Cardiology Clinics:

* Adults aged \>18 years
* Known type 2 diabetes
* Previous acute coronary syndrome within the last 10 years but \> 6 months ago
* Taking one or more oral hypoglycaemic agent and /or GLP1 receptor analogue, and/or insulin

Exclusion Criteria:

From the Hammersmith Hospital In-patient Cardiology Services:

* HbA1c \<48mmol/mol
* People who have previously had bariatric surgery
* People taking hydroxyurea
* People who undergo haemodialysis or peritoneal dialysis
* Unable to participate due to other factors, as assessed by the Chief Investigators
* Pregnancy as determined by clinical team
* Known to have a terminal condition or conditions that suggest a life expectancy less than 1 year

From Imperial College Healthcare Trust Diabetes and Cardiology Clinics:

* HbA1c \<48mmol/mol
* People who have previously had bariatric surgery
* People taking hydroxyurea
* People who undergo haemodialysis or peritoneal dialysis
* Unable to participate due to other factors, as assessed by the Chief Investigators
* Pregnancy as determined by clinical team
* Known to have a terminal condition or conditions that suggest a life expectancy less than 1 year
* Previous acute coronary syndrome more than 10 years ago or within the last 6 months

Withdrawal criteria

* The subject has a serious event related to the study
* Investigated initiated discontinuation of study due to participation or equipment concerns
* Withdrawal of consent

Primary outcomes:
measure: Primary outcome: Percent time spent in glucose target range (3.9-10mmol/L)
timeFrame: 26 weeks
Secondary outcomes:
measure: Number hypoglycaemic excursions.
timeFrame: 26 weeks
measure: Time spent in hypoglycaemia (<3.9mmol/L, 70mg/dL; <3.0mmol/L, 54mg/dL),
timeFrame: 26 weeks
measure: Time in euglycaemia (3.9-7.8mmol/L, 70-140mg/dL).
timeFrame: 26 weeks
measure: Time in hyperglycaemia (>10mmol/L, 180mg/dL).
timeFrame: 26 weeks
measure: Hypoglycaemia requiring 3rd party assistance.
timeFrame: 26 weeks
measure: Number hypoglycaemic excursions (sensor glucose <3.0mmol/l for >= 20min)
timeFrame: 26 weeks
measure: HbA1c at 12 weeks and 26 weeks.
timeFrame: 26 weeks
measure: Glucose variability assessed by %Coefficient of Variation (%CV).
timeFrame: 26 weeks
measure: Mean Absolute Glucose (MAG)
timeFrame: 26 weeks
measure: Health and treatment-related quality of life measured by the Diabetes Treatment Satisfaction Scale score.
timeFrame: 26 weeks
measure: Hypoglycaemic symptoms
timeFrame: 26 weeks.
measure: Low Blood Glucose Index (LBGI})
timeFrame: 26 weeks.
measure: Audit of Diabetes Dependent Quality of Life questionnaire domain.
timeFrame: 26 weeks.
Other outcomes:
measure: MACE endpoint defined as death due to cardiac cause or hospitalisation with acute coronary syndrome (including MI and unstable angina); heart failure; unscheduled revascularisation; arrhythmia; cerebrovascular event
timeFrame: 26 weeks
measure: All cause mortality
timeFrame: 26 weeks
measure: Duration of hospital admission before 'medically fit for discharge'.
timeFrame: 26 weeks
measure: Escalation to High Dependency Unit or Intensive Care Unit during primary hospital episode.
timeFrame: 26 weeks
measure: Echocardiographic measurements of cardiac function.
timeFrame: 26 weeks
measure: Changes in care, measured by changes in diabetes medication usage.
timeFrame: 26 weeks
Locations:
city: London
country: United Kingdom
facility: Hammersmith Hospital inpatient cardiology services
Study officials:
affiliation: Imperial College London
name: Monika Reddy, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: Jamil Mayet, MBChB, MD
role: PRINCIPAL_INVESTIGATOR
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