Insulin Degludec for the Management of Patient With Recurrent Diabetic Ketoacidosis

NCT ID: NCT03001323

Last Updated: 2021-05-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-31

Study Completion Date

2020-09-25

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Given the longer half life of insulin degludec compared to glargine /levemir ,investigators believe that insulin degludec will reduce the rate of recurrent DKA. The investigator will randomize participants to control and intervention group. Control group will receive Lantus/Levemir and intervention group will receive degludec. The investigators will call participants monthly and see them in the clinic every three months.The investigators will follow them for 1 year and evaluate if there will be a difference in rate of DKA in between these two groups.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Hypothesis:

Use of a longer-lasting basal insulin (degludec) in patients with recurrent Diabetic Ketoacidosis (DKA) will reduce the rate of recurrent DKA and improve adherence to daily administration in patients who have had 2 or more episode of DKA in the past 2 years.

STUDY DESIGN AND METHODS:

Patients admitted with Diabetic Ketoacidosis (DKA) to Hennepin County Medical Center (HCMC) who have a prior episode of DKA within 2 years will be offered enrollment in a prospective, randomized unblinded trial to determine whether long acting insulin degludec will reduce the rate of recurrent DKA and improve compliance over the period of 1 year when compared with the control group who will stay on their pre-study long acting insulin (glargine or detemir).

Primary Outcomes:

To determine the difference in rate of recurrent Diabetic Ketoacidosis (DKA) over 6 months and 12 months in participants who have a history of previous DKA and medication adherence between groups treated with degludec vs other long-acting insulins (glargine or detemir).

Secondary outcomes:

BG control (Hba1c during study period) tested q 3 months Discharge long-acting insulin dose compared to admission dose LOS for DKA admission Number of readmissions in one year Number of ER visits Hypoglycemia -self reported, documented by glucometer or ER visit for severe hypoglycemia Adherence to study regimen from phone call information and clinic visits

Inclusion criteria:

Patients age \>18 year with previous diagnosis of Diabetes Mellitus and previous admission for DKA in any facility within the prior 2 years who meet the criteria for DKA at the time of admission and are willing to participate in the study protocol will be enrolled in the study.

DKA is defined as:

1. Serum bicarbonate below 18 mg/dl
2. Anion Gap over greater than or equal to 16
3. Serum ketones or beta hydroxybutyrate elevation \> 3 mmol/L
4. Serum glucose greater than or equal to 250 mg/dl

Exclusion Criteria: Patients with no previous DKA, patients who are not willing to consent to participate in the study protocol for 1 year, pregnant women, dementia, and end stage renal disease on dialysis.

Study Protocol:

Investigators will obtain informed consent and enroll participants admitted to the Hennepin County Medical Center (HCMC) in this study from Jan 2016 until investigators have adequate enrollment.

Investigators will collect the initial data as following:

1. Age, sex, height, weight, BMI
2. Age at diagnosis of diabetes
3. Number previous DKA admissions in past 2 years, lifetime (even if the admission was to other hospitals)
4. Preadmission insulin dosing - long acting
5. Reason for DKA
6. Alcohol, drug use, homelessness, mental illness
7. Admission labs - HCO3, AG, BOHB, glucose, creatinine
8. Length of stay with each DKA episode( LOS)

The participants will be randomly assign to the intervention or control groups.

Intervention Group:

Discharge on once a day degludec insulin by pen (supplied by Novo) at dose 0.3 U/kg with reduction to 0.2 U/kg for GFR \<30 ml/hr. Degludec insulin will be started at study initiation during the hospitalization if the participant is randomized to this arm.

Fast acting insulin that participant is using will be adjusted so that total daily dose given to cover 2 or 3 meals is equal to the long-acting insulin dose. Participants will have basal bolus regimen either using carbohydrate counting or with set doses for meals, depending on their ability. Participants will use the fast acting insulin they were on at the time of admission.

Insulin adjustment if hypoglycemia (less than 60 mg/dl) or if fasting BG over 140 despite insulin compliance. For hypoglycemia, dose will be lowered 0.05 U/kg and for elevated fasting glucose it will be raised 0.05 U/kg.

Phone calls every month to check on dose, compliance, hospital admissions, and hypoglycemia. Compliance with medication will be verified verbally.

Clinic visits every 3 months for 1 year with dose adjustment as above. Supply adequate insulin degludec until next visit.

Control Group:

Discharge on 0.3 U/kg of admission long acting insulin glargine or detemir (provided by diabetes and endocrine clinic) regardless of participant's home insulin regimen at the time of admission with reduction to 0.2 U/kg in CKD with GFR \<30 ml/hr. This will be done at the time of study initiation during the hospitalization if the participant is randomized to this arm.

Fast acting insulin adjustment with meals and insulin adjustment for hypoglycemia will be done similarly as in the intervention group. Phone calls every month to check on dose, compliance, hospital admissions, and hypoglycemia. Compliance will be assessed verbally.

Clinic visits every 3 months for 1 year with insulin dose adjustment as above. Supply adequate insulin glargine or detemir until next visit.

Study site: Hennepin County Medical Center (HCMC), Minneapolis, MN.

Data Analysis: Sample size, power calculation and statistical plan

Investigators determined that considering incidence of DKA 100 % (since all patients admitted with DKA would be eligible for screening), moreover, in order to observe 30 % reduction in DKA related hospitalization over 2 years period in intervention group and by keeping power at 80 % with confidence interval (CI) of 0.05, study will need to enroll 21 subjects in each group or 42 total sample size.

In order to mitigate the effects of loss to follow up, noncompliance and protocol deviations, intention to treat (ITT) analysis will be performed on primary and secondary outcome measure for both groups. A separate analysis will be done including those patient who will complete the trial in both groups.

Baseline data of intervention and control group will be compared. In case of significant differences, further analysis will be done to adjust for those differences prior to final analysis.

ITT analysis will be based on in ITT comparison.

Descriptive and inferential statistical methods will be used for analyzing the data using Statistical Analysis software (SAS) 9.4. For continuous variables, mean, median and variance will be reported, while for discrete variables rate, risk ratios, relative risk, rate of occurrence and percentage differences will be reported.

For primary outcome measure, investigators will use χ2 test to assess relationship between the primary outcome and some of the binary nature secondary measures. Stratification will be used for analysis as needed. In that case, chi-square tests for overall and within relevant stratifications will be conducted. To assess the difference between continuous variables (such as hemoglobin A1C, bicarbonate, anion gap, Creatinine etc.), t-test will be used for normally distributed data. Otherwise Mann-Whitney U test will be used. P-values at 95 % CI will be reported. Since it is a superiority trial, we will use one-tail test for significance.

.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Diabetes Mellitus

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Degludec

Discharge on once a day degludec insulin by pen (supplied by Novo) at dose 0.3 U/kg with reduction to 0.2 U/kg for GFR \<30 ml/hr.

Group Type EXPERIMENTAL

Degludec

Intervention Type DRUG

Discharge on once a day degludec insulin by pen (supplied by Novo) at dose 0.3 U/kg with reduction to 0.2 U/kg for GFR \<30 ml/hr.

Fast acting insulin that patient is using will be adjusted so that total daily dose given to cover 2 or 3 meals is equal to the long-acting insulin dose. Patient will have basal bolus regimen either using carb counting or with set doses for meals.

Insulin adjustment if hypoglycemia (less than 60 mg/dl) or if fasting BG over 140 despite insulin compliance. For hypoglycemia, dose will be lowered 0.05 U/kg and for elevated fasting glucose it will be raised 0.05 U/kg.

Phone calls every month and clinic visits every 3 months for 1 year with dose adjustment as above.

Standard long-acting

Discharge on 0.3 U/kg of admission long acting insulin glargine or detemir (provided by diabetes and endocrine clinic) regardless of their home insulin regimen at the time of admission with reduction to 0.2 U/kg in CKD with GFR \<30 ml/hr.

Group Type ACTIVE_COMPARATOR

Standard long-acting

Intervention Type DRUG

Discharge on once a day long-acting insulin by pen that patient is using at time of enrollment (supplied by clinic) at dose 0.3 U/kg with reduction to 0.2 U/kg for GFR \<30 ml/hr.

Fast acting insulin that patient is using will be adjusted so that total daily dose given to cover 2 or 3 meals is equal to the long-acting insulin dose. Patient will have basal bolus regimen either using carb counting or with set doses for meals.

Insulin adjustment if hypoglycemia (less than 60 mg/dl) or if fasting BG over 140 despite insulin compliance. For hypoglycemia, dose will be lowered 0.05 U/kg and for elevated fasting glucose it will be raised 0.05 U/kg.

Phone calls every month and clinic visits every 3 months for 1 year with dose adjustment as above.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Degludec

Discharge on once a day degludec insulin by pen (supplied by Novo) at dose 0.3 U/kg with reduction to 0.2 U/kg for GFR \<30 ml/hr.

Fast acting insulin that patient is using will be adjusted so that total daily dose given to cover 2 or 3 meals is equal to the long-acting insulin dose. Patient will have basal bolus regimen either using carb counting or with set doses for meals.

Insulin adjustment if hypoglycemia (less than 60 mg/dl) or if fasting BG over 140 despite insulin compliance. For hypoglycemia, dose will be lowered 0.05 U/kg and for elevated fasting glucose it will be raised 0.05 U/kg.

Phone calls every month and clinic visits every 3 months for 1 year with dose adjustment as above.

Intervention Type DRUG

Standard long-acting

Discharge on once a day long-acting insulin by pen that patient is using at time of enrollment (supplied by clinic) at dose 0.3 U/kg with reduction to 0.2 U/kg for GFR \<30 ml/hr.

Fast acting insulin that patient is using will be adjusted so that total daily dose given to cover 2 or 3 meals is equal to the long-acting insulin dose. Patient will have basal bolus regimen either using carb counting or with set doses for meals.

Insulin adjustment if hypoglycemia (less than 60 mg/dl) or if fasting BG over 140 despite insulin compliance. For hypoglycemia, dose will be lowered 0.05 U/kg and for elevated fasting glucose it will be raised 0.05 U/kg.

Phone calls every month and clinic visits every 3 months for 1 year with dose adjustment as above.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Patients age \>18 year with previous diagnosis of Diabetes Mellitus and previous admission for DKA in any facility within the prior 2 years who meet the criteria for DKA at the time of admission and are willing to participate in the study protocol will be enrolled in the study.

DKA is defined as:

1. Serum bicarbonate below 18 mg/dl
2. Anion Gap over greater than or equal to 16
3. Serum ketones or beta hydroxybutyrate elevation \> 3 mmol/L
4. Serum glucose greater than or equal to 250 mg/dl

Exclusion Criteria

Patients with no previous DKA, patients who are not willing to consent to participate in the study protocol for 1 year, pregnant women, dementia, and end stage renal disease on dialysis.

\-
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Hennepin Healthcare Research Institute

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Related Links

Access external resources that provide additional context or updates about the study.

http://rdcu.be/nOo3

Risk related with DKA - mortality related to DKA

https://www.ncbi.nlm.nih.gov/pubmed/21775761

Analysis of socioeconomic and psychological factors to analyze factors leading to insulin non compliance.

https://www.ncbi.nlm.nih.gov/pubmed/23757621

To identify the factors that influence recurrent (one or more previous episodes) diabetic ketoacidosis (DKA), which we refer to as recurrent DKA.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

HRS#16-4236

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

IDegLira HIGH Trial
NCT03737240 COMPLETED PHASE3
Insulin Glargine Versus Twice-Daily NPH
NCT00687453 TERMINATED PHASE4