<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03001323</url>
  </required_header>
  <id_info>
    <org_study_id>HRS#16-4236</org_study_id>
    <nct_id>NCT03001323</nct_id>
  </id_info>
  <brief_title>Insulin Degludec for the Management of Patient With Recurrent Diabetic Ketoacidosis</brief_title>
  <official_title>Insulin Degludec for the Management of Patient With Recurrent Diabetic Ketoacidosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hennepin Healthcare Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hennepin Healthcare Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Given the longer half life of insulin degludec compared to glargine /levemir ,investigators&#xD;
      believe that insulin degludec will reduce the rate of recurrent DKA. The investigator will&#xD;
      randomize participants to control and intervention group. Control group will receive&#xD;
      Lantus/Levemir and intervention group will receive degludec. The investigators will call&#xD;
      participants monthly and see them in the clinic every three months.The investigators will&#xD;
      follow them for 1 year and evaluate if there will be a difference in rate of DKA in between&#xD;
      these two groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypothesis:&#xD;
&#xD;
      Use of a longer-lasting basal insulin (degludec) in patients with recurrent Diabetic&#xD;
      Ketoacidosis (DKA) will reduce the rate of recurrent DKA and improve adherence to daily&#xD;
      administration in patients who have had 2 or more episode of DKA in the past 2 years.&#xD;
&#xD;
      STUDY DESIGN AND METHODS:&#xD;
&#xD;
      Patients admitted with Diabetic Ketoacidosis (DKA) to Hennepin County Medical Center (HCMC)&#xD;
      who have a prior episode of DKA within 2 years will be offered enrollment in a prospective,&#xD;
      randomized unblinded trial to determine whether long acting insulin degludec will reduce the&#xD;
      rate of recurrent DKA and improve compliance over the period of 1 year when compared with the&#xD;
      control group who will stay on their pre-study long acting insulin (glargine or detemir).&#xD;
&#xD;
      Primary Outcomes:&#xD;
&#xD;
      To determine the difference in rate of recurrent Diabetic Ketoacidosis (DKA) over 6 months&#xD;
      and 12 months in participants who have a history of previous DKA and medication adherence&#xD;
      between groups treated with degludec vs other long-acting insulins (glargine or detemir).&#xD;
&#xD;
      Secondary outcomes:&#xD;
&#xD;
      BG control (Hba1c during study period) tested q 3 months Discharge long-acting insulin dose&#xD;
      compared to admission dose LOS for DKA admission Number of readmissions in one year Number of&#xD;
      ER visits Hypoglycemia -self reported, documented by glucometer or ER visit for severe&#xD;
      hypoglycemia Adherence to study regimen from phone call information and clinic visits&#xD;
&#xD;
      Inclusion criteria:&#xD;
&#xD;
      Patients age &gt;18 year with previous diagnosis of Diabetes Mellitus and previous admission for&#xD;
      DKA in any facility within the prior 2 years who meet the criteria for DKA at the time of&#xD;
      admission and are willing to participate in the study protocol will be enrolled in the study.&#xD;
&#xD;
      DKA is defined as:&#xD;
&#xD;
        1. Serum bicarbonate below 18 mg/dl&#xD;
&#xD;
        2. Anion Gap over greater than or equal to 16&#xD;
&#xD;
        3. Serum ketones or beta hydroxybutyrate elevation &gt; 3 mmol/L&#xD;
&#xD;
        4. Serum glucose greater than or equal to 250 mg/dl&#xD;
&#xD;
      Exclusion Criteria: Patients with no previous DKA, patients who are not willing to consent to&#xD;
      participate in the study protocol for 1 year, pregnant women, dementia, and end stage renal&#xD;
      disease on dialysis.&#xD;
&#xD;
      Study Protocol:&#xD;
&#xD;
      Investigators will obtain informed consent and enroll participants admitted to the Hennepin&#xD;
      County Medical Center (HCMC) in this study from Jan 2016 until investigators have adequate&#xD;
      enrollment.&#xD;
&#xD;
      Investigators will collect the initial data as following:&#xD;
&#xD;
        1. Age, sex, height, weight, BMI&#xD;
&#xD;
        2. Age at diagnosis of diabetes&#xD;
&#xD;
        3. Number previous DKA admissions in past 2 years, lifetime (even if the admission was to&#xD;
           other hospitals)&#xD;
&#xD;
        4. Preadmission insulin dosing - long acting&#xD;
&#xD;
        5. Reason for DKA&#xD;
&#xD;
        6. Alcohol, drug use, homelessness, mental illness&#xD;
&#xD;
        7. Admission labs - HCO3, AG, BOHB, glucose, creatinine&#xD;
&#xD;
        8. Length of stay with each DKA episode( LOS)&#xD;
&#xD;
      The participants will be randomly assign to the intervention or control groups.&#xD;
&#xD;
      Intervention Group:&#xD;
&#xD;
      Discharge on once a day degludec insulin by pen (supplied by Novo) at dose 0.3 U/kg with&#xD;
      reduction to 0.2 U/kg for GFR &lt;30 ml/hr. Degludec insulin will be started at study initiation&#xD;
      during the hospitalization if the participant is randomized to this arm.&#xD;
&#xD;
      Fast acting insulin that participant is using will be adjusted so that total daily dose given&#xD;
      to cover 2 or 3 meals is equal to the long-acting insulin dose. Participants will have basal&#xD;
      bolus regimen either using carbohydrate counting or with set doses for meals, depending on&#xD;
      their ability. Participants will use the fast acting insulin they were on at the time of&#xD;
      admission.&#xD;
&#xD;
      Insulin adjustment if hypoglycemia (less than 60 mg/dl) or if fasting BG over 140 despite&#xD;
      insulin compliance. For hypoglycemia, dose will be lowered 0.05 U/kg and for elevated fasting&#xD;
      glucose it will be raised 0.05 U/kg.&#xD;
&#xD;
      Phone calls every month to check on dose, compliance, hospital admissions, and hypoglycemia.&#xD;
      Compliance with medication will be verified verbally.&#xD;
&#xD;
      Clinic visits every 3 months for 1 year with dose adjustment as above. Supply adequate&#xD;
      insulin degludec until next visit.&#xD;
&#xD;
      Control Group:&#xD;
&#xD;
      Discharge on 0.3 U/kg of admission long acting insulin glargine or detemir (provided by&#xD;
      diabetes and endocrine clinic) regardless of participant's home insulin regimen at the time&#xD;
      of admission with reduction to 0.2 U/kg in CKD with GFR &lt;30 ml/hr. This will be done at the&#xD;
      time of study initiation during the hospitalization if the participant is randomized to this&#xD;
      arm.&#xD;
&#xD;
      Fast acting insulin adjustment with meals and insulin adjustment for hypoglycemia will be&#xD;
      done similarly as in the intervention group. Phone calls every month to check on dose,&#xD;
      compliance, hospital admissions, and hypoglycemia. Compliance will be assessed verbally.&#xD;
&#xD;
      Clinic visits every 3 months for 1 year with insulin dose adjustment as above. Supply&#xD;
      adequate insulin glargine or detemir until next visit.&#xD;
&#xD;
      Study site: Hennepin County Medical Center (HCMC), Minneapolis, MN.&#xD;
&#xD;
      Data Analysis: Sample size, power calculation and statistical plan&#xD;
&#xD;
      Investigators determined that considering incidence of DKA 100 % (since all patients admitted&#xD;
      with DKA would be eligible for screening), moreover, in order to observe 30 % reduction in&#xD;
      DKA related hospitalization over 2 years period in intervention group and by keeping power at&#xD;
      80 % with confidence interval (CI) of 0.05, study will need to enroll 21 subjects in each&#xD;
      group or 42 total sample size.&#xD;
&#xD;
      In order to mitigate the effects of loss to follow up, noncompliance and protocol deviations,&#xD;
      intention to treat (ITT) analysis will be performed on primary and secondary outcome measure&#xD;
      for both groups. A separate analysis will be done including those patient who will complete&#xD;
      the trial in both groups.&#xD;
&#xD;
      Baseline data of intervention and control group will be compared. In case of significant&#xD;
      differences, further analysis will be done to adjust for those differences prior to final&#xD;
      analysis.&#xD;
&#xD;
      ITT analysis will be based on in ITT comparison.&#xD;
&#xD;
      Descriptive and inferential statistical methods will be used for analyzing the data using&#xD;
      Statistical Analysis software (SAS) 9.4. For continuous variables, mean, median and variance&#xD;
      will be reported, while for discrete variables rate, risk ratios, relative risk, rate of&#xD;
      occurrence and percentage differences will be reported.&#xD;
&#xD;
      For primary outcome measure, investigators will use χ2 test to assess relationship between&#xD;
      the primary outcome and some of the binary nature secondary measures. Stratification will be&#xD;
      used for analysis as needed. In that case, chi-square tests for overall and within relevant&#xD;
      stratifications will be conducted. To assess the difference between continuous variables&#xD;
      (such as hemoglobin A1C, bicarbonate, anion gap, Creatinine etc.), t-test will be used for&#xD;
      normally distributed data. Otherwise Mann-Whitney U test will be used. P-values at 95 % CI&#xD;
      will be reported. Since it is a superiority trial, we will use one-tail test for&#xD;
      significance.&#xD;
&#xD;
      .&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Enrollment was too low to provide statistically significant data&#xD;
  </why_stopped>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">September 25, 2020</completion_date>
  <primary_completion_date type="Actual">January 20, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reduction in frequency of diabetic ketoacidosis</measure>
    <time_frame>6 and 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>A1c(Hemoglobin A1c) level Discharge long-acting insulin dose compared to admission dose LOS for DKA admission Number of readmissions in one year Number of ER visits Hypoglycemia</measure>
    <time_frame>1yr -every 3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypoglycemia frequency and severity</measure>
    <time_frame>1 yr</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>length of stay for Diabetic ketoacidosis(LOS)</measure>
    <time_frame>1 yr</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emergency room visit reduction for diabetes</measure>
    <time_frame>1 yr</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Readmission to the hospital frequency</measure>
    <time_frame>1 yr</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Basal insulin requirements</measure>
    <time_frame>1 yr</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Degludec</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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 &lt;30 ml/hr.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard long-acting</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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 &lt;30 ml/hr.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Degludec</intervention_name>
    <description>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 &lt;30 ml/hr.&#xD;
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.&#xD;
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.&#xD;
Phone calls every month and clinic visits every 3 months for 1 year with dose adjustment as above.</description>
    <arm_group_label>Degludec</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard long-acting</intervention_name>
    <description>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 &lt;30 ml/hr.&#xD;
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.&#xD;
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.&#xD;
Phone calls every month and clinic visits every 3 months for 1 year with dose adjustment as above.</description>
    <arm_group_label>Standard long-acting</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients age &gt;18 year with previous diagnosis of Diabetes Mellitus and previous admission&#xD;
        for DKA in any facility within the prior 2 years who meet the criteria for DKA at the time&#xD;
        of admission and are willing to participate in the study protocol will be enrolled in the&#xD;
        study.&#xD;
&#xD;
        DKA is defined as:&#xD;
&#xD;
          1. Serum bicarbonate below 18 mg/dl&#xD;
&#xD;
          2. Anion Gap over greater than or equal to 16&#xD;
&#xD;
          3. Serum ketones or beta hydroxybutyrate elevation &gt; 3 mmol/L&#xD;
&#xD;
          4. Serum glucose greater than or equal to 250 mg/dl&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients with no previous DKA, patients who are not willing to consent to participate in&#xD;
        the study protocol for 1 year, pregnant women, dementia, and end stage renal disease on&#xD;
        dialysis.&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hennepin County Medical Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55415</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://cdc.gov/nchs/about/major/hdasd/nhds.htm</url>
    <description>Increasing incidence of DKA</description>
  </link>
  <link>
    <url>http://rdcu.be/nOo3</url>
    <description>Risk related with DKA - mortality related to DKA</description>
  </link>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/19564476</url>
    <description>Hyperglycemic crisis</description>
  </link>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/21775761</url>
    <description>Analysis of socioeconomic and psychological factors to analyze factors leading to insulin non compliance.</description>
  </link>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/23757621</url>
    <description>To identify the factors that influence recurrent (one or more previous episodes) diabetic ketoacidosis (DKA), which we refer to as recurrent DKA.</description>
  </link>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/25179915</url>
    <description>Degludec pharmacology</description>
  </link>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/labs/articles/26773446/</url>
    <description>Safety and efficacy of degludec</description>
  </link>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 19, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 23, 2016</study_first_posted>
  <last_update_submitted>May 13, 2021</last_update_submitted>
  <last_update_submitted_qc>May 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketosis</mesh_term>
    <mesh_term>Diabetic Ketoacidosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>August 26, 2021</submitted>
    <returned>September 22, 2021</returned>
    <submitted>August 23, 2022</submitted>
    <returned>September 15, 2022</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03001323
org study id: HRS#16-4236
nct id: NCT03001323
lead sponsor: 
has dmc: No
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.
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.

      .
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Reduction in frequency of diabetic ketoacidosis
time frame: 6 and 12 months
measure: A1c(Hemoglobin A1c) level Discharge long-acting insulin dose compared to admission dose LOS for DKA admission Number of readmissions in one year Number of ER visits Hypoglycemia
time frame: 1yr -every 3 months
measure: Hypoglycemia frequency and severity
time frame: 1 yr
measure: length of stay for Diabetic ketoacidosis(LOS)
time frame: 1 yr
measure: Emergency room visit reduction for diabetes
time frame: 1 yr
measure: Readmission to the hospital frequency
time frame: 1 yr
measure: Basal insulin requirements
time frame: 1 yr
arm group label: Degludec
arm group type: Experimental
description: 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.
arm group label: Standard long-acting
arm group type: Active Comparator
description: 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.
intervention type: Drug
intervention name: Degludec
description: 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.
arm group label: Degludec
intervention type: Drug
intervention name: Standard long-acting
description: 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.
arm group label: Standard long-acting
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
url: http://cdc.gov/nchs/about/major/hdasd/nhds.htm
description: Increasing incidence of DKA
url: http://rdcu.be/nOo3
description: Risk related with DKA - mortality related to DKA
url: https://www.ncbi.nlm.nih.gov/pubmed/19564476
description: Hyperglycemic crisis
url: https://www.ncbi.nlm.nih.gov/pubmed/21775761
description: Analysis of socioeconomic and psychological factors to analyze factors leading to insulin non compliance.
url: https://www.ncbi.nlm.nih.gov/pubmed/23757621
description: To identify the factors that influence recurrent (one or more previous episodes) diabetic ketoacidosis (DKA), which we refer to as recurrent DKA.
url: https://www.ncbi.nlm.nih.gov/pubmed/25179915
description: Degludec pharmacology
url: https://www.ncbi.nlm.nih.gov/labs/articles/26773446/
description: Safety and efficacy of degludec
responsible party type: Sponsor
mesh term: Ketosis
mesh term: Diabetic Ketoacidosis
sharing ipd: No
submitted: August 26, 2021
returned: September 22, 2021
submitted: August 23, 2022
returned: September 15, 2022