Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001158459
Ethics application status
Approved
Date submitted
20/08/2016
Date registered
25/08/2016
Date last updated
18/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparison of the incidence and duration of hypoglycaemia assessed by Continuous Glucose Monitoring (CGM) in elderly type 2 Diabetes patients treated with two different insulin regimens (long and short acting insulin VS premixed insulin) .
Scientific title
Comparison of the incidence and duration of hypoglycaemia assessed by Continuous Glucose Monitoring (CGM) in patients aged 65 years or older with Type 2 Diabetes (T2D), treated with Insulin Glargine (Toujeo) and Insulin Glulisine (Apidra) Versus Twice – Daily Premixed Insulin.

Secondary ID [1] 289961 0
Funding company (Sanofi Australia) trial number
GLARGL08042
Universal Trial Number (UTN)
U1111-1186-7004
Trial acronym
“CHAMPION”, for short!

(C)omparison of the incidence and duration of (h)ypoglycaemia (a)ssessed by Continuous Glucose (M)onitoring (CGM) in ( p)atients aged 65 years or older with Type 2 Diabetes (T2D), treated with (I)nsulin Glargine (Touje(o)) and Insulin Glulisine (Apidra) Versus Twice – Daily Premixed Insuli(n).
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type two Diabetes Mellitus 299951 0
Hypoglycaemia in elderly type two Diabetes Mellitus patients on premixed insulin treatment 299952 0
Condition category
Condition code
Metabolic and Endocrine 299850 299850 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Visit 1 :
1.Dietary history, Dietician review and education for healthy lifestyle and eating. Subjects will not be asked to perform complex carbohydrate counting, but will receive a standard healthy meal plan appropriate for age and activity, containing moderate amounts of regularly-spaced carbohydrates, weighted towards the morning and evening meals. (30 minutes one to one session)
2.Diabetes educator review to ensure uniformity of blood glucose monitoring and insulin injection technique and review (30 minutes one to one session)
3.Supply of Self monitored blood glucose meter ,blood glucose strips and blood glucose record booklet. Participants will be requested to record blood sugar level four times a day for a week (Before meals and before bed)
4.Supply of dietary diary book to record all dietary intake for one week.
5.Participants will undergo Diabetes Quality of Life Questionnaire, which has been validated for the use in T2DM patients..
Visit 2, Follow up visit in one-week time:
1. Participants who showed consistency in recording blood sugar levels and dietary intake as requested would undergo seven consecutive days of CGM (Medtronic, Registered Trademark). This CGM system does not reveal blood glucose results in real-time to either the wearer or clinician. CGM device will be inserted subcutaneously at the clinic. Participants will also continue to record their Blood glucose levels and dietary intake in week 2
2. All participants will continue during this first CGM week on their preexisting twice-daily pre mixed insulin.
3. Participants will be booked for visit at day 7 of CGM insertion for removal of the CGM.
Visit 3, one-week time from visit 2
1.Following removal of CGM, results will be reviewed by an independent health professional not otherwise involved in the study analysis to ensure that there are no recorded severe hypoglycaemic episodes (Interstitial glucose <2.5 mmol/L at any time).
2.Participants who show evidence of severe hypoglycaemia on CGM will have CGM results unblinded to the investigators for further management and insulin adjustment. They will remain in the study. In all other cases, investigators will not know the results of initial CGM until the conclusion of the study.
3.Participants will be randomized from the time of this visit by allocating the next available randomization number to the participant and allocating a treatment sequence using a computer-generated code. Stratification will be done based on two criteria, HbA1c (6.5-8.4 and 8.5 -10) and age (65-75 and >75).
4.42 Participants will be randomised to each arm, one arm will continue on their pre-existing twice daily premixed insulin and the other arm will be allocated to Basal insulin glargine plus two bolus insulin glulisine injections with the two main meals . Patients who will require different Basal Bolus regimen due to their different dietary requirements will be allowed to switch to Basal plus either 1, 2 or maximum 3 boluses of Insulin during the titration phase.
5.Insuline dosages will be decided by the principal or co investigators who are Endocrinologists or Endocrinology registrars . Insulin Glargine initial dose will be 80% of the total units per day of intermediate insulin portion of their current premixed insulin.
6.Insulin Glargine dose will represent 1/3 to 1/2 of the total daily insulin requirements for participants switched to the basal bolus regimen depending on their dietary pattern and carbohydrate intake.
7.The remaining insulin requirements will be provided as two boluses of Insulin Glulisine with the two main meals aiming for two injection times per day where one bolus will be injected with one of the two main meals and the other bolus injection will be injected at the same time as the basal insulin with the other main meal, however participants will be allowed to switch to either one, two or three boluses of insulin depending on their dietary need.
8.On the same visit, participants who have been randomized to basal plus regimen arm will undergo an educational session one to one by Dietician and Diabetic educator for one hour to discuss meal plans and insulin plan for their new regimen.
9.Participants will be requested to attend four weekly visits for stabilization and optimization of blood glucose level control aiming for fasting blood glucose level of 4-8 mmol/l and postprandial blood glucose level of 6-12 mmol/l.
10.The participants will be allowed to continue with their current stable doses of oral hypoglycaemic medications throughout the whole study period.
Visit 4, 5, 6 and 7, four weeks Stabilization period for both arms
1.Weekly visit for individualised optimization of blood glucose level aiming for a target fasting blood glucose level of 4-8 mmol/l and postprandial level of 6-12 mmol/l.
2. Participants who are progressing satisfactorily towards target within the four week period will be managed in the community with a dose titration plan for their insulin for a further 12 week treatment period for each arm and to be reviewed in 12 weeks’ time.
3.Participants who have ongoing poor blood glucose control or hypoglycaemia after 4 weeks will undergo continued weekly review until levels are stabilised.Those extended weekly review will be during the 12 weeks treatment period. which is fixed period to all participants.
Treatment period, 12 weeks' community based period:
1.Participants in both arms will continue to record their self-monitored blood glucose level 4 times a day during the 12 weeks treatment period.
2.Participants will be encouraged to contact the research team for phone advice regarding their Diabetes management and insulin dose titration
3.Participants will be requested to return to the University and research centre clinic at the end of week 12 to repeat CGM
Visit 8, End of treatment period visit and scheduled repeated unblinded CGM:
1. All Participants will repeat the Diabetes Quality of Life Questionnaire
2. CGM will be inserted for a planned 7 consecutive days
3. Participants will continue to record their self-monitored blood glucose level plus dietary intake during the CGM week period, and to maintain a similar lifestyle to their first CGM period.
4.Participants will continue during this week on their randomly allocated treatment
Visit 9, Final visit:
1.CGM removal and reviewing dietary and self-monitored blood glucose levels
2.Repeating HbA1c, Fructosamine, Full blood count , Liver function test and kidney function test.
3.Participants will be allowed by the end of this visit to choose their preferred insulin regimen; participants who will choose to continue on Basal Bolus regimen will continue to have their insulin supplied through subsequent GP management and prescription.
Intervention code [1] 295677 0
Treatment: Drugs
Comparator / control treatment
The active control group will be the participants who continued their pre-existing premixed insulin during the 12 weeks treatment period to compare them versus the other group of participants who will be switched to basal plus insulin regimen during the same treatment period .
Control group
Active

Outcomes
Primary outcome [1] 299358 0
-Compare the percentage of time spent in hypoglycemia, as determined by continuous glucose monitoring (percentage of time spent with interstitial glucose < 3.9 mmol/l during a 7 day CGM test) between the two interventions.
Timepoint [1] 299358 0
Primary outcome will be assessed at the end of study period following the second CGM assessment which will be at the end of visit 9 which is by the end of 7 days of the second CGM assessment (at the end of the 7 days following the 12 weeks treatment period)
CGM data will include the two CGM done during the study period
Secondary outcome [1] 326919 0
CGM analysis of variability and peaks (MAGE and SD ) between the two interventions using CGM data that will be done twice during the study period
Timepoint [1] 326919 0
will be assessed one at the end of the study period which will be by the end of the second CGM which is by the end of the 7 days CGM assessment after the 12 weeks treatment period.
Assessment will be based on the CGM data for the two CGM done during this study
Secondary outcome [2] 326980 0
2-Assess number of episodes of hypoglycemia using the CGM data and documented self monitored blood glucose finger bricks .
Timepoint [2] 326980 0
will be assessed at the end of the study period which will be by the end of the second CGM which is by the end of the 7 days CGM assessment after the 12 weeks treatment period.

Assessment will be done using the CGM data and self monitored blood sugar levels
Secondary outcome [3] 326981 0
Assess insulin requirements (total daily dosage) for the two interventions, assess basal and prandial insulin requirements in the basal plus arm .
Assessment will be done using the daily insulin administration reported by the participants and recorded in the blood sugar booklet
Timepoint [3] 326981 0
will be assessed at the end of the study period which will be by the end of the second CGM which is by the end of the 7 days CGM assessment after the 12 weeks treatment period.

Assessment will be done using the current insulin does reported by the participant at the end of the trial.
Secondary outcome [4] 326982 0
4-Assess morbidity data including cardiac events, frequency of hospital admissions due to hypoglycaemic episodes, falls and fall related complications in the two interventions as a composite end point . Assessment will be done using medical records and self reported events by the participants .
Timepoint [4] 326982 0
will be assessed at the end of the study period which will be by the end of the second CGM which is by the end of the 7 days CGM assessment after the 12 weeks treatment period.

Assessment will be done through collecting history of any medical events during the treatment period.
Secondary outcome [5] 326983 0
5-Assess patient QOL in the two interventions.
Timepoint [5] 326983 0
Quality of life evaluation will be assessed by the end of week 18 of the whole study period which is at visit 8 by the end of the 12 weeks treatment period and before commencing the second CGM -The quality of life questionnaire going to be used is QUALITY OF LIFE INDEX-Diabetes version. The questionnaire has been validated in previous studies as a suitable tool to assess quality of life in Diabetes patients.
Secondary outcome [6] 327011 0
6-Assess HBA1C in the two interventions using a serum blood test
Timepoint [6] 327011 0
will be assessed twice , one at visit 0 which is the screening visit and one at the end of the study period which will be by the end of the second CGM which is by the end of the 7 days CGM assessment after the 12 weeks treatment period.
Assessment will be done using serum blood tests.
Secondary outcome [7] 327012 0
7-Assess Fructosamine in the two interventions using a serum blood test
Timepoint [7] 327012 0
will be assessed twice , one at visit 0 which is the screening visit and one at the end of the study period which will be by the end of the second CGM which is by the end of the 7 days CGM assessment after the 12 weeks treatment period.
Assessment will be done using serum and blood tests.
Secondary outcome [8] 327013 0
8-Assess time spent in hypoglycemia during day time (06:00 am –24:00) in the two interventions using CGM data
Timepoint [8] 327013 0
will be assessed during the two CGM periods, for 7 days at baseline and for 7 days immediately following the 12 week treatment period
Secondary outcome [9] 327014 0
10-Assesstime spent in hypoglycemia during night time (24:00 -06:00 am ) in the two interventions
Timepoint [9] 327014 0
will be assessed during the two CGM periods, for 7 days at baseline and for 7 days immediately following the 12 week treatment period .
Secondary outcome [10] 329506 0
Number of severe episodes of hypoglycemia assessed by requiring third party assistance or associated with a loss of consciousness or severe consequences.
This outcome will be assessed by direct reporting of the participants on each visit and by regular check of the medical records during the study period
Timepoint [10] 329506 0
Will be assessed during the 12 weeks interventional period using the daily blood sugar booklet record which will be assessed by the end of the 12 weeks period
Secondary outcome [11] 329507 0
Incidence of hypoglycemia episodes <3.9mmol/l, 3.1 mmol/L and <2.0mmol,as assessed by Self Monitored Blood Glucose (SMBG)
Timepoint [11] 329507 0
Will be assessed during the 12 weeks interventional period using the daily blood sugar booklet which will be assessed at the end of the 12 weeks period
Secondary outcome [12] 329508 0
Incidence of hypoglycemia episodes <3.9mmol/l, 3.1 mmol/L and <2.0mmol,as assessed by Self Monitored Blood Glucose (SMBG).

This outcome will be assessed during the 12 weeks treatment period using the daily blood sugar booklet at the end of the 12 weeks period
Timepoint [12] 329508 0
Will be assessed during the 12 weeks interventional period
Secondary outcome [13] 329509 0
Assess percentage of time spent in blood glucose target range in the two interventions using the continuous glucose monitoring
Timepoint [13] 329509 0
During the two CGM periods.will be assessed during the two CGM periods, for 7 days at baseline and for 7 days immediately following the 12 week treatment period
Secondary outcome [14] 329510 0
Assess number of symptomatic hypoglycemia episodes in the two interventions. will be assessed using the medical records and direct reporting from the patients during the study visits
Timepoint [14] 329510 0
During the two CGM periods.will be assessed during the two CGM periods, for 7 days at baseline and for 7 days immediately following the 12 week treatment period

Eligibility
Key inclusion criteria
Inclusion criteria:
1- T2DM patients
2- Age 65 year or older
3- On twice daily premixed Insulin
4-HbA1c at the time of enrolment: 6.5 to 10 %
5- On stable doses of oral hypoglycemic medications in the preceding 3 months before study enrolment
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria:
1- T1DM Patients
2- Patients on long-term glucocorticoids or potential glucocorticoid treatment during the study period
3-Anemia or known history of significant haematological disorders
4-End stage renal disease on renal replacement therapy
5-End stage liver disease
6-Documented history of cognitive impairment or mental health disorders
7- History of severe and recurrent documented hypoglycemia.
8- Residents of high level aged care facilities
9-Active malignancy (other than Squamous cell carcinoma and basal cell carcinoma).

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment will be done using central randomisation by a computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation will be done on visit 3 by the next available randomization number to the participant and allocating a treatment sequence using a computer-generated code. Stratification will be done based on two criteria, HbA1c (6.5-8.4 and 8.5 -10) and age (65-75 and >75
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
-A previous study of CGM in subjects on pre-mixed insulin with baseline HbA1c 6.5% to 8.5% demonstrated an average 4% mean of total time spent in hypoglycaemia (Interstitial glucose <3.5). We calculate that randomising eighty four subjects (42 in each arm) will have an 85% power to detect a 30% reduction (5% to 3.5%) in the percentage time spent in hypoglycaemia (tissue glucose <3.9 mmol/L) of subjects on pre mixed insulin during 7 days CGM test in comparison with subjects on basal bolus insulin. The sample size has a
two sided significance level of 5% and allows for 10% of patients not being followed and 5% of patients crossing between the two interventions.

-Analyses will be carried out on an intention to treat basis. The distribution of the primary
outcome will be assessed and if as expected, it has a Poisson distribution it will be analyzed using a generalized linear model. The distribution of all continuous variables will be assessed. Normally distributed variables will be summarized with means and standard deviations and compared between the interventions using t-tests or general linear models. Non-normal variables will be summarized using medians and inter-quartile ranges and compared using a Wilcoxon test or other non-parametric test or transformed and analyzed as a normal variable. Binary outcomes will be summarized with percent and compared using chi-square tests. Models for binary outcomes will use a generalized linear models.

-After 6 months the power and sample size can be reassessed based on the percentage time spent in hypoglycaemia from the whole study and the original assumption that the control group will spend 5% of time in hypoglycaemia, or on a different control value if information external to the study becomes available

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
28/11/2016
Actual
17/01/2017
Date of last participant enrolment
Anticipated
30/06/2019
Actual
Date of last data collection
Anticipated
31/03/2020
Actual
Sample size
Target
84
Accrual to date
16
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 6514 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 6515 0
Mount Druitt Hospital - Mount Druitt
Recruitment postcode(s) [1] 14078 0
2148 - Blacktown
Recruitment postcode(s) [2] 14079 0
2770 - Mount Druitt

Funding & Sponsors
Funding source category [1] 294355 0
Commercial sector/Industry
Name [1] 294355 0
Sanofi Australia
Country [1] 294355 0
Australia
Primary sponsor type
Government body
Name
Western Sydney Local Health District
Address
PO Box 574 Wentworthville NSW 2145
Australia
Country
Australia
Secondary sponsor category [1] 293194 0
None
Name [1] 293194 0
Address [1] 293194 0
Country [1] 293194 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295773 0
Western Sydney Local health District Research and Education Network
Ethics committee address [1] 295773 0
Westmead Hospital
cnr Hawkesbury and Darcy Rds
Westmead
NSW 2145
Ethics committee country [1] 295773 0
Australia
Date submitted for ethics approval [1] 295773 0
13/04/2016
Approval date [1] 295773 0
18/07/2016
Ethics approval number [1] 295773 0
4666 AU RED HREC/16/WMEAD/128

Summary
Brief summary
Aims of the study:
1-To compare the number of episodes of hypoglycaemia, and time spent in hypoglycaemia between a pre-mixed insulin regimen and a basal-plus 2, Toujeo-based regimen in an elderly population with T2DM using CGM.
2-To compare total insulin requirements, measures of glucose variability and glycaemic control, weight gain and other health-related outcomes between the two insulin regimens.
3-Assess the impact on quality of life in elderly T2DM patients switching from pre mixed insulin to a basal-plus 2 regimen.
4-Assess the incidence and rate of hypoglycemia reported by Self Monitored Blood Glucose (SMBG) during the treatment periods of non CGM recording


-Hypothesis:

We postulate that hypoglycaemia (interstitial glucose <3.9, or critically <2.5 mmol/l) assessed by (CGM) will remain more prevalent in patients continuing biphasic insulin, compared with those switching to a basal-plus 2 insulin regimen.

We hypothesise that subjects switched to a basal-plus 2 regimen will have reduced glycaemic variability and lower insulin requirements.

We further postulate that switching to a basal-plus 2 insulin regimen will be not inferior to premixed insulin in term of quality of life (QOL).

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68354 0
Prof Mark Mclean
Address 68354 0
Blacktown hospital
Blacktown Road
Blacktown , NSW 2148
Country 68354 0
Australia
Phone 68354 0
+61 2 98516073
Fax 68354 0
+61 2 98516050
Email 68354 0
marck.mclean@health.nsw.gov.au
Contact person for public queries
Name 68355 0
Dr Ahmed Hussein
Address 68355 0
Endocrinology Department -Blacktown Hospital
Blacktown Road
Blacktown
NSW 2148
Country 68355 0
Australia
Phone 68355 0
+61448917337
Fax 68355 0
Email 68355 0
ahmedalsaeed_79@hotmail.com
Contact person for scientific queries
Name 68356 0
Prof Mark Mclean
Address 68356 0
Blacktown hospital
Blacktown Road
Blacktown , NSW 2148
Country 68356 0
Australia
Phone 68356 0
+61 2 98516073
Fax 68356 0
+61 2 98516050
Email 68356 0
marck.mclean@health.nsw.gov.au

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No Supporting Document Provided


Results publications and other study-related documents

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