Ignite Creation Date:
2024-05-06 @ 4:55 PM
Last Modification Date:
2024-10-26 @ 2:18 PM
Study NCT ID:
NCT05135676
Status:
COMPLETED
Last Update Posted:
2024-03-22
First Post:
2021-10-21
Brief Title:
Time in Glucose Hospital Target
Sponsor:
Jaeb Center for Health Research
Organization:
Jaeb Center for Health Research
Study Overview
Official Title:
Time in Glucose Hospital Target TIGHT - A Randomized Clinical Trial to Evaluate the Use of CGM to Achieve a Mean Glucose Target of 90 to 130 mgdL Without Hypoglycemia in Hospitalized Adults With Type 2 Diabetes
Status:
COMPLETED
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TIGHT
Brief Summary:
Inpatient management of glycemia in people with diabetes has been inadequately studied Previous randomized trials of intensive insulin therapy in the hospital setting resulted in excessive hypoglycemia Current ADA guidelines glucose 140-180 mgdL are by consensus with the upper bound defined by observational data and the lower bound by safety concerns None of the previous studies of intensive glucose management used CGM technology Whether near normal glucose levels can be achieved without increasing hypoglycemia among hospitalized patients with diabetes with the advent of CGM technology is not known
There are clear associations between hyperglycemia and poor outcomes in patients with diabetes hospitalized with infection including COVID-19 The COVID-19 pandemic has increased the urgency to definitively answer the question of whether glucose lowering below 140-180 mgdL can be achieved without increasing hypoglycemia
If this proposed study demonstrates intensive management of glucose to a target of 90 to 130 mgdL without hypoglycemia is achievable in the inpatient setting with CGM technology a larger study could then be performed to evaluate whether there is clinical benefit including a reduction in morbidity and mortality
The primary study hypothesis is that glucose management with CGM can achieve a mean glucose of 90-130 mgdL without increasing hypoglycemia compared with standard care with a glucose target of 140-180 mgdL Individuals with diabetes who are hospitalized non-ICU for an eligible condition will be randomly assigned to receive standard therapy glucose target 140-180 mgdL per ADA guidelines or intensive therapy glucose target 90-130 mgdL and CGM used for monitoring Real-time CGM will be used in the Intensive Target Group and masked CGM will be used in the Standard Target Group
The co-primary outcomes assessed via a hierarchical approach include a treatment group comparison of mean glucose superiority followed by a non-inferiority comparison of time 54 mgdL measured with CGM
There are clear associations between hyperglycemia and poor outcomes in patients with diabetes hospitalized with infection including COVID-19 The COVID-19 pandemic has increased the urgency to definitively answer the question of whether glucose lowering below 140-180 mgdL can be achieved without increasing hypoglycemia
If this proposed study demonstrates intensive management of glucose to a target of 90 to 130 mgdL without hypoglycemia is achievable in the inpatient setting with CGM technology a larger study could then be performed to evaluate whether there is clinical benefit including a reduction in morbidity and mortality
The primary study hypothesis is that glucose management with CGM can achieve a mean glucose of 90-130 mgdL without increasing hypoglycemia compared with standard care with a glucose target of 140-180 mgdL Individuals with diabetes who are hospitalized non-ICU for an eligible condition will be randomly assigned to receive standard therapy glucose target 140-180 mgdL per ADA guidelines or intensive therapy glucose target 90-130 mgdL and CGM used for monitoring Real-time CGM will be used in the Intensive Target Group and masked CGM will be used in the Standard Target Group
The co-primary outcomes assessed via a hierarchical approach include a treatment group comparison of mean glucose superiority followed by a non-inferiority comparison of time 54 mgdL measured with CGM
Detailed Description:
Protocol Overview
The glucose management team GMT at each site will identify potentially eligible patients
After informed consent and confirmation of eligibility each participant will be randomly assigned to the Standard Target or Intensive Target group
Glucose management in the Standard Target Group will follow the hospitals usual practice using insulin for glucose management with a target glucose concentration of 140-180 mgdL
- A masked CGM sensor will be worn
Glucose management in the Intensive Target Group will include close monitoring by the site GMT to maximize the percentage of glucose values in the range of 90 to 130 mgdL
Glucose monitoring will include real-time CGM The hospitals GMT will be the ones monitoring the CGM data The information from CGM will be used for future management changes to insulin delivery and for safety monitoring particularly for hypoglycemia In essence CGM will be used adjunctively in the study
CGM validation will occur within 2-6 hours following sensor insertion and must be within 20 of a blood glucose result of 100 mgdL for two consecutive blood glucose measurements If a blood glucose result is 100 mgdL the corresponding CGM reading must be within 20 mgdL of the blood glucose value CGM validation will occur at least twice daily
Insulin delivery will be based on the sites usual protocol The hospital nursing staff will follow their institutional SOPs with respect to frequency of BGM testing and use of BG test results for administering meal insulin and corrections The nursing staff will not be utilizing CGM in this regard
Study participation will conclude at the time of hospital discharge 10 days after randomization at time of transfer to ICU or death
Quality Assurance Plan
Designated personnel from the Coordinating Center will be responsible for maintaining quality assurance QA and quality control QC systems to ensure that the clinical portion of the trial is conducted and data are generated documented and reported in compliance with the protocol Good Clinical Practice GCP and the applicable regulatory requirements as well as to ensure that the rights and wellbeing of trial participants are protected and that the reported trial data are accurate complete and verifiable Eligibility informed consent data entry completion and adverse events will be prioritized for monitoring
Source Data Verification
Study data will be obtained from the participant the participants EHR and from CGM EHR data will be either transcribed from the EHR onto eCRFs on the study website or will be electronically transmitted to the Coordinating Center
Standard Operating Procedures
1 Patient Recruitment and Enrollment
Recruitment will involve identification of hospitalized patients at each clinical center who meet the study eligibility criteria There will be no specific efforts to promote recruitment other than making hospital staff aware of the study
Enrollment will proceed with the goal of at least 120 participants entering the randomized trial but no greater than 150 Screening for eligibility will be performed from medical records prior to informed consent being signed Thus once informed consent is signed randomization will proceed quickly Participants who have signed consent may be permitted to continue into the trial if eligible even if the randomization goal has been reached
Study participants will be recruited from 3-6 clinical centers in the United States All eligible participants will be included without regard to sex race or ethnicity There is no restriction on the number of participants to be enrolled by each site toward the overall recruitment goal
2 Data Collection and Testing
After informed consent has been signed all potential participants who are females of child-bearing potential will have a serum or urine pregnancy test if one has not been done since hospital admission
Data from the EHR will be recorded in the study database Medical history information will include diabetes history other medical conditions medications height and weight HbA1c during hospitalization or most recent prior to admission and other relevant laboratory values The medical condition that prompted hospital admission will be recorded
3 Data Recorded for Study in addition to data collected at enrollment
At the end of hospitalization or 10 days from randomization data to be recorded will include
Vitals blood pressure heart rate temperature and O2 saturation if oxygen is used
BGM
Insulin received each day type of insulin route IV or SQ of units
All medical conditions that developed during the hospitalization
Date of transfer to ICU
Medications received
All coded discharge diagnoses including alive or dead
Labs if measuredavailable such as
At admission and prior to randomization if available
Hematocrit and hemoglobin
Electrolytes sodium potassium bicarbonate
Liver function ALT
COVID-19 testing
All measurements at admission and while active in the study
Glucose
HbA1c
CreatinineeGFR
4 Reporting for Adverse Events
SAEs possibly related to a study device or study participation and UADEs must be reported to the Coordinating Center within 24 hours of the site becoming aware of the event This can occur via phone or email or by completion of the online serious adverse event form and device issue form if applicable If the form is not initially completed it should be competed as soon as possible after there is sufficient information to evaluate the event All other reportable ADEs and other reportable AEs should be submitted by completion on the on line form within 7 days of the site becoming aware of the event The Coordinating Center will notify all participating investigators of any adverse event that is serious related and unexpected Notification will be made within 10 working days after the Coordinating Center becomes aware of the event Each principal investigator is responsible for reporting serious study-related adverse events and abiding by any other reporting requirements specific to hisher Institutional Review Board or Ethics Committee Where the JCHR IRB is the overseeing IRB sites must report all serious related adverse events within seven calendar days Upon receipt of a qualifying event the Sponsor will investigate the event to determine if a UADE is confirmed and if indicated report the results of the investigation to all overseeing IRBs and the FDA within 10 working days of the Sponsor becoming aware of the UADE per 21CFR 81246b The Medical Monitor must determine if the UADE presents an unreasonable risk to participants If so the Medical Monitor must ensure that all investigations or parts of investigations presenting that risk are terminated as soon as possible but no later than 5 working days after the Medical Monitor makes this determination and no later than 15 working days after first receipt notice of the UADE
Sample Size
Sample size has been computed for the treatment group comparison of mean glucose
A total sample size was computed to be N110 for the following assumptions two randomized arms 90 power a 25 mgdL difference in mean glucose between treatment groups SD of 40 mgdL and 2-sided type 1 error of 005
The total sample size has been increased to N150 to account for potential dropouts and incomplete CGM glucose data due to early hospital discharge
For percent of time 54 mgdL statistical power will be 99 for demonstrating non-inferiority two randomized arms a total sample size of N110 a standard deviation of 1 no difference and alpha 0025
Statistical Analysis Plan
The trial has co-primary outcomes measured using CGM for up to 10 days following randomization mean glucose tested between groups for superiority and time 54 mgdL tested to demonstrate non-inferiority of intensive treatment compared with standard treatment The intervention will be considered effective only if both endpoints are met
The nullalternative hypotheses are
1 Mean Glucose
1 Null Hypothesis There is no difference in mean glucose between Standard and Intensive groups
2 Alternative Hypothesis The mean glucose is different in the Standard and Intensive groups
2 Percent Time 54 mgdL
1 Null Hypothesis There is an absolute mean difference of at least 1 in the percent time 54 mgdL between the Intensive and Standard group
2 Alternative Hypothesis There is an absolute mean difference of less than 1 in the percent time 54 mgdL between the Intensive and Standard groups
The glucose management team GMT at each site will identify potentially eligible patients
After informed consent and confirmation of eligibility each participant will be randomly assigned to the Standard Target or Intensive Target group
Glucose management in the Standard Target Group will follow the hospitals usual practice using insulin for glucose management with a target glucose concentration of 140-180 mgdL
- A masked CGM sensor will be worn
Glucose management in the Intensive Target Group will include close monitoring by the site GMT to maximize the percentage of glucose values in the range of 90 to 130 mgdL
Glucose monitoring will include real-time CGM The hospitals GMT will be the ones monitoring the CGM data The information from CGM will be used for future management changes to insulin delivery and for safety monitoring particularly for hypoglycemia In essence CGM will be used adjunctively in the study
CGM validation will occur within 2-6 hours following sensor insertion and must be within 20 of a blood glucose result of 100 mgdL for two consecutive blood glucose measurements If a blood glucose result is 100 mgdL the corresponding CGM reading must be within 20 mgdL of the blood glucose value CGM validation will occur at least twice daily
Insulin delivery will be based on the sites usual protocol The hospital nursing staff will follow their institutional SOPs with respect to frequency of BGM testing and use of BG test results for administering meal insulin and corrections The nursing staff will not be utilizing CGM in this regard
Study participation will conclude at the time of hospital discharge 10 days after randomization at time of transfer to ICU or death
Quality Assurance Plan
Designated personnel from the Coordinating Center will be responsible for maintaining quality assurance QA and quality control QC systems to ensure that the clinical portion of the trial is conducted and data are generated documented and reported in compliance with the protocol Good Clinical Practice GCP and the applicable regulatory requirements as well as to ensure that the rights and wellbeing of trial participants are protected and that the reported trial data are accurate complete and verifiable Eligibility informed consent data entry completion and adverse events will be prioritized for monitoring
Source Data Verification
Study data will be obtained from the participant the participants EHR and from CGM EHR data will be either transcribed from the EHR onto eCRFs on the study website or will be electronically transmitted to the Coordinating Center
Standard Operating Procedures
1 Patient Recruitment and Enrollment
Recruitment will involve identification of hospitalized patients at each clinical center who meet the study eligibility criteria There will be no specific efforts to promote recruitment other than making hospital staff aware of the study
Enrollment will proceed with the goal of at least 120 participants entering the randomized trial but no greater than 150 Screening for eligibility will be performed from medical records prior to informed consent being signed Thus once informed consent is signed randomization will proceed quickly Participants who have signed consent may be permitted to continue into the trial if eligible even if the randomization goal has been reached
Study participants will be recruited from 3-6 clinical centers in the United States All eligible participants will be included without regard to sex race or ethnicity There is no restriction on the number of participants to be enrolled by each site toward the overall recruitment goal
2 Data Collection and Testing
After informed consent has been signed all potential participants who are females of child-bearing potential will have a serum or urine pregnancy test if one has not been done since hospital admission
Data from the EHR will be recorded in the study database Medical history information will include diabetes history other medical conditions medications height and weight HbA1c during hospitalization or most recent prior to admission and other relevant laboratory values The medical condition that prompted hospital admission will be recorded
3 Data Recorded for Study in addition to data collected at enrollment
At the end of hospitalization or 10 days from randomization data to be recorded will include
Vitals blood pressure heart rate temperature and O2 saturation if oxygen is used
BGM
Insulin received each day type of insulin route IV or SQ of units
All medical conditions that developed during the hospitalization
Date of transfer to ICU
Medications received
All coded discharge diagnoses including alive or dead
Labs if measuredavailable such as
At admission and prior to randomization if available
Hematocrit and hemoglobin
Electrolytes sodium potassium bicarbonate
Liver function ALT
COVID-19 testing
All measurements at admission and while active in the study
Glucose
HbA1c
CreatinineeGFR
4 Reporting for Adverse Events
SAEs possibly related to a study device or study participation and UADEs must be reported to the Coordinating Center within 24 hours of the site becoming aware of the event This can occur via phone or email or by completion of the online serious adverse event form and device issue form if applicable If the form is not initially completed it should be competed as soon as possible after there is sufficient information to evaluate the event All other reportable ADEs and other reportable AEs should be submitted by completion on the on line form within 7 days of the site becoming aware of the event The Coordinating Center will notify all participating investigators of any adverse event that is serious related and unexpected Notification will be made within 10 working days after the Coordinating Center becomes aware of the event Each principal investigator is responsible for reporting serious study-related adverse events and abiding by any other reporting requirements specific to hisher Institutional Review Board or Ethics Committee Where the JCHR IRB is the overseeing IRB sites must report all serious related adverse events within seven calendar days Upon receipt of a qualifying event the Sponsor will investigate the event to determine if a UADE is confirmed and if indicated report the results of the investigation to all overseeing IRBs and the FDA within 10 working days of the Sponsor becoming aware of the UADE per 21CFR 81246b The Medical Monitor must determine if the UADE presents an unreasonable risk to participants If so the Medical Monitor must ensure that all investigations or parts of investigations presenting that risk are terminated as soon as possible but no later than 5 working days after the Medical Monitor makes this determination and no later than 15 working days after first receipt notice of the UADE
Sample Size
Sample size has been computed for the treatment group comparison of mean glucose
A total sample size was computed to be N110 for the following assumptions two randomized arms 90 power a 25 mgdL difference in mean glucose between treatment groups SD of 40 mgdL and 2-sided type 1 error of 005
The total sample size has been increased to N150 to account for potential dropouts and incomplete CGM glucose data due to early hospital discharge
For percent of time 54 mgdL statistical power will be 99 for demonstrating non-inferiority two randomized arms a total sample size of N110 a standard deviation of 1 no difference and alpha 0025
Statistical Analysis Plan
The trial has co-primary outcomes measured using CGM for up to 10 days following randomization mean glucose tested between groups for superiority and time 54 mgdL tested to demonstrate non-inferiority of intensive treatment compared with standard treatment The intervention will be considered effective only if both endpoints are met
The nullalternative hypotheses are
1 Mean Glucose
1 Null Hypothesis There is no difference in mean glucose between Standard and Intensive groups
2 Alternative Hypothesis The mean glucose is different in the Standard and Intensive groups
2 Percent Time 54 mgdL
1 Null Hypothesis There is an absolute mean difference of at least 1 in the percent time 54 mgdL between the Intensive and Standard group
2 Alternative Hypothesis There is an absolute mean difference of less than 1 in the percent time 54 mgdL between the Intensive and Standard groups
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None