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A Comparison of Two Treatment Strategies in Older Participants With Type 2 Diabetes Mellitus (T2DM) (IMPERIUM)

Primary Purpose

Diabetes Mellitus, Type 2

Status

Terminated

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

Glimepiride

Metformin

Pioglitazone

Acarbose

Linagliptin

Sitagliptin

Liraglutide

Insulin Glargine

Exenatide once weekly (QW)

Exenatide twice daily (BID)

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Have T2DM based on a history and clinical impression that is consistent with the World Health Organization (WHO) Classification of Diabetes
Have a Clinical Frailty Scale (CFS) score of 4 or above or Total Illness Burden Index (TIBI) score of 5 or above as assessed at screening
Have an A1c >7.3% and <10.9% at study entry and are not achieving desired glycemic control as evidenced by A1c measurement at least 0.4% higher than individualized treatment target set at screening.
Have been treated for at least 3 months prior to the study entry with any of the following treatment options:
- Diet/exercise only (only if they have known contraindications to metformin treatment)
- Any dose of sulfonylurea
- Effective or maximally-tolerated doses of metformin, dipeptidyl-peptidase-4 (DPP-4) inhibitor, thiazolidinedione, or acarbose used in monotherapy or in dual combination. The following doses are considered to be effective:
  - at least 1500 mg of metformin per day
  - At least 30 mg of pioglitazone per day
  - At least 4 mg of rosiglitazone per day
  - At least 75 mg of acarbose per day
  - Any marketed dose of DPP-4 inhibitor

Exclusion Criteria:

Are currently enrolled in a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Have participated, within the last 60 days in a clinical trial involving an investigational product other than the investigational product used in this study. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed
Have previously completed or withdrawn from this study. This exclusion criterion does not apply to participants who are rescreened prior to randomization
At study entry, have contraindications to sulfonylurea, insulin, or GLP-1 RA
Have a history of pancreatitis, a personal or family history of medullary thyroid carcinoma, or have Multiple Endocrine Neoplasia syndrome type 2
Have taken any injectable glucose-lowering agent, miglitol, meglitinide, Sodium/Glucose cotransporter-2 inhibitor, or other antihyperglycemia treatment that is not listed in the fourth inclusion criterion for more than 10 days within 3 months prior to the study entry
In the opinion of investigator should have an individualized A1c target set at 8% or higher
Have a body mass index (BMI) greater than 45 kg/m^2
Have had more than 1 episode of severe hypoglycemia within 24 weeks prior to the study
Have cardiac disease with functional status that is Class III or IV according to the New York Heart Association Cardiac Disease Classification
Have an estimated glomerular filtration rate (eGFR) <30 milliliter/minute/1.73 m^2 (mL/min/1.73 m^2) or advanced renal disease including history of renal transplantation or currently receiving renal dialysis
Have obvious clinical signs or symptoms or laboratory evidence of liver disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 2.5 times the upper limit of the reference range)
Receive current therapy for a malignancy, other than basal-cell or squamous-cell skin cancer
Received systemic glucocorticoids within the 3 months prior to entry for more than 14 consecutive days
Have any other condition that precludes the participant from following and completing the study

Sites / Locations

Suncoast Research Group, LLC
New Horizon Research Center
Suncoast Clinical Research
Florida Hospital
Athens Primary Care
Herman Clinical Research, LLC
Rocky Mountain Diabetes and Osteoporosis Center
Iderc, P.L.C.
Cotton O'Neil Clinic
Mercy Health Research
Southern New Hampshire Diabetes and Endocrinology
Heritage Valley Medical Group, Inc.
Family Medical Associates
Carolina Health Specialists
Dallas Diabetes Endocrine Center
Rockwood Clinic Research Center
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Manati Medical Center
American Telemedicine Center
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Strategy A (Glucose-Dependent)

Strategy B (Reference)

Arm Description

Participants may receive oral and injectable (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) therapies that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks.

Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Insulin glargine is titrated according treatment algorithm. Treatment may last up to 72 weeks.

Outcomes

Primary Outcome Measures

Percentage of Participants Achieving and Maintaining Individualized Glycated Hemoglobin A1c (HbA1c) Targets Without Clinically Significant Hypoglycemia

Failed to reach and maintain HbA1c target, without clinically significant hypoglycemia, is defined as having 2 consecutive HbA1c > upper limit of HbA1c target over 12 weeks starting from Week 24 for participants with HbA1c data beyond Week 24, or Week 24 HbA1c > upper limit of HbA1c target for participants without HbA1c data beyond Week 24. Clinically significant hypoglycemia is defined as any severe hypoglycemia or repeated hypoglycemia interrupting participants activities or sleep and associated with blood glucose ≤3.9 millimole per liter (mmol/L), or repeated asymptomatic hypoglycemia associated with blood glucose <3.0 mmol/L. Success is defined as lacking of failure.

Secondary Outcome Measures

Percentage of Participants Requiring Alternative Treatment Due to Glycemic Failure of First Line Injectable Therapy

Number of Participants With Total Hypoglycemia and Other Categories of Hypoglycemia

Change From Baseline of Urinary Albumin to Creatinine Ratio

The Urinary Albumin to Creatinine Ratio is used in addition to Estimated Glomerular Filtration Rate (eGFR) to measure the incidence and progression of diabetic kidney disease.

Change From Baseline in Body Mass Index (BMI)

Change From Baseline of Estimated Glomerular Filtration Rate (eGFR)

The eGFR is used in addition to the Urinary Albumin to Creatinine Ratio to measure the incidence and progression of diabetic kidney disease.

Full Information

NCT ID

NCT02072096

First Posted

February 24, 2014

Last Updated

September 25, 2019

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT02072096

Brief Title

A Comparison of Two Treatment Strategies in Older Participants With Type 2 Diabetes Mellitus (T2DM)

Acronym

IMPERIUM

Official Title

An Individualized treatMent aPproach for oldER patIents: A Randomized, Controlled stUdy in Type 2 Diabetes Mellitus (IMPERIUM)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Terminated

Why Stopped

The trial was terminated per protocol because of lack of feasibility.

Study Start Date

February 2014 (undefined)

Primary Completion Date

October 2015 (Actual)

Study Completion Date

October 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The main purpose of this study is to compare the benefits and risks associated with the use of 2 treatment strategies to lower blood sugar in participants aged 65 and older with T2DM. One strategy is based on the use of oral and injectable medications that only reduce blood sugar (glucose) when it is high. The other strategy is based on non-glucose dependent agents. The trial will last up to 72 weeks for each participant.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

192 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Strategy A (Glucose-Dependent)

Arm Type

Experimental

Arm Description

Arm Title

Strategy B (Reference)

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Glimepiride

Intervention Description

Administered orally

Intervention Type

Drug

Intervention Name(s)

Metformin

Intervention Description

Administered orally

Intervention Type

Drug

Intervention Name(s)

Pioglitazone

Intervention Description

Administered orally

Intervention Type

Drug

Intervention Name(s)

Acarbose

Intervention Description

Administered orally

Intervention Type

Drug

Intervention Name(s)

Linagliptin

Intervention Description

Administered orally

Intervention Type

Drug

Intervention Name(s)

Sitagliptin

Intervention Description

Administered orally

Intervention Type

Drug

Intervention Name(s)

Liraglutide

Intervention Description

Administered subcutaneously (SC)

Intervention Type

Drug

Intervention Name(s)

Insulin Glargine

Intervention Description

Administered SC

Intervention Type

Drug

Intervention Name(s)

Exenatide once weekly (QW)

Intervention Description

Administered SC

Intervention Type

Drug

Intervention Name(s)

Exenatide twice daily (BID)

Intervention Description

Administered SC

Primary Outcome Measure Information:

Title

Percentage of Participants Achieving and Maintaining Individualized Glycated Hemoglobin A1c (HbA1c) Targets Without Clinically Significant Hypoglycemia

Description

Time Frame

Baseline to last participant visit (up to 72 weeks)

Secondary Outcome Measure Information:

Title

Percentage of Participants Requiring Alternative Treatment Due to Glycemic Failure of First Line Injectable Therapy

Time Frame

Baseline to last participant visit (up to 72 weeks)

Title

Number of Participants With Total Hypoglycemia and Other Categories of Hypoglycemia

Time Frame

Baseline to last participant visit (up to 72 weeks)

Title

Change From Baseline of Urinary Albumin to Creatinine Ratio

Description

The Urinary Albumin to Creatinine Ratio is used in addition to Estimated Glomerular Filtration Rate (eGFR) to measure the incidence and progression of diabetic kidney disease.

Time Frame

Baseline, Week 72

Title

Change From Baseline in Body Mass Index (BMI)

Time Frame

Baseline, Week 72

Title

Change From Baseline of Estimated Glomerular Filtration Rate (eGFR)

Description

The eGFR is used in addition to the Urinary Albumin to Creatinine Ratio to measure the incidence and progression of diabetic kidney disease.

Time Frame

Baseline, Week 72

Other Pre-specified Outcome Measures:

Title

Change From Baseline in Adult Low Blood Sugar Survey (ALBSS) Score

Time Frame

Baseline, Week 72

Title

Change From Baseline in European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Score

Time Frame

Baseline, Week 72

Title

Change From Baseline in Mini-mental State Examination (MMSE) Score

Time Frame

Baseline, Week 72

10. Eligibility

Sex

All

Minimum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Have T2DM based on a history and clinical impression that is consistent with the World Health Organization (WHO) Classification of Diabetes Have a Clinical Frailty Scale (CFS) score of 4 or above or Total Illness Burden Index (TIBI) score of 5 or above as assessed at screening Have an A1c >7.3% and <10.9% at study entry and are not achieving desired glycemic control as evidenced by A1c measurement at least 0.4% higher than individualized treatment target set at screening. Have been treated for at least 3 months prior to the study entry with any of the following treatment options: Diet/exercise only (only if they have known contraindications to metformin treatment) Any dose of sulfonylurea Effective or maximally-tolerated doses of metformin, dipeptidyl-peptidase-4 (DPP-4) inhibitor, thiazolidinedione, or acarbose used in monotherapy or in dual combination. The following doses are considered to be effective: at least 1500 mg of metformin per day At least 30 mg of pioglitazone per day At least 4 mg of rosiglitazone per day At least 75 mg of acarbose per day Any marketed dose of DPP-4 inhibitor Exclusion Criteria: Are currently enrolled in a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study Have participated, within the last 60 days in a clinical trial involving an investigational product other than the investigational product used in this study. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed Have previously completed or withdrawn from this study. This exclusion criterion does not apply to participants who are rescreened prior to randomization At study entry, have contraindications to sulfonylurea, insulin, or GLP-1 RA Have a history of pancreatitis, a personal or family history of medullary thyroid carcinoma, or have Multiple Endocrine Neoplasia syndrome type 2 Have taken any injectable glucose-lowering agent, miglitol, meglitinide, Sodium/Glucose cotransporter-2 inhibitor, or other antihyperglycemia treatment that is not listed in the fourth inclusion criterion for more than 10 days within 3 months prior to the study entry In the opinion of investigator should have an individualized A1c target set at 8% or higher Have a body mass index (BMI) greater than 45 kg/m^2 Have had more than 1 episode of severe hypoglycemia within 24 weeks prior to the study Have cardiac disease with functional status that is Class III or IV according to the New York Heart Association Cardiac Disease Classification Have an estimated glomerular filtration rate (eGFR) <30 milliliter/minute/1.73 m^2 (mL/min/1.73 m^2) or advanced renal disease including history of renal transplantation or currently receiving renal dialysis Have obvious clinical signs or symptoms or laboratory evidence of liver disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 2.5 times the upper limit of the reference range) Receive current therapy for a malignancy, other than basal-cell or squamous-cell skin cancer Received systemic glucocorticoids within the 3 months prior to entry for more than 14 consecutive days Have any other condition that precludes the participant from following and completing the study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

Suncoast Research Group, LLC

City

Miami

State/Province

Florida

ZIP/Postal Code

33135

Country

United States

Facility Name

New Horizon Research Center

City

Miami

State/Province

Florida

ZIP/Postal Code

33175

Country

United States

Facility Name

Suncoast Clinical Research

City

New Port Richey

State/Province

Florida

ZIP/Postal Code

34652

Country

United States

Facility Name

Florida Hospital

City

Orlando

State/Province

Florida

ZIP/Postal Code

32804

Country

United States

Facility Name

Athens Primary Care

City

Athens

State/Province

Georgia

ZIP/Postal Code

30606

Country

United States

Facility Name

Herman Clinical Research, LLC

City

Suwanee

State/Province

Georgia

ZIP/Postal Code

30024

Country

United States

Facility Name

Rocky Mountain Diabetes and Osteoporosis Center

City

Idaho Falls

State/Province

Idaho

ZIP/Postal Code

83404

Country

United States

Facility Name

Iderc, P.L.C.

City

Des Moines

State/Province

Iowa

ZIP/Postal Code

50314

Country

United States

Facility Name

Cotton O'Neil Clinic

City

Topeka

State/Province

Kansas

ZIP/Postal Code

66606

Country

United States

Facility Name

Mercy Health Research

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63141

Country

United States

Facility Name

Southern New Hampshire Diabetes and Endocrinology

City

Nashua

State/Province

New Hampshire

ZIP/Postal Code

03063

Country

United States

Facility Name

Heritage Valley Medical Group, Inc.

City

Beaver

State/Province

Pennsylvania

ZIP/Postal Code

15009

Country

United States

Facility Name

Family Medical Associates

City

Levittown

State/Province

Pennsylvania

ZIP/Postal Code

19056

Country

United States

Facility Name

Carolina Health Specialists

City

Myrtle Beach

State/Province

South Carolina

ZIP/Postal Code

29572

Country

United States

Facility Name

Dallas Diabetes Endocrine Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75230

Country

United States

Facility Name

Rockwood Clinic Research Center

City

Spokane

State/Province

Washington

ZIP/Postal Code

99202

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

City

Saint Stefan Ob Stainz

ZIP/Postal Code

A-8511

Country

Austria

Facility Name

City

Salzburg

ZIP/Postal Code

5026

Country

Austria

Facility Name

City

Vienna

ZIP/Postal Code

A-1060

Country

Austria

Facility Name

City

Wien

ZIP/Postal Code

A 1210

Country

Austria

Facility Name

City

Berlin

ZIP/Postal Code

10409

Country

Germany

Facility Name

City

Dortmund

ZIP/Postal Code

44137

Country

Germany

Facility Name

City

Hamburg

ZIP/Postal Code

22607

Country

Germany

Facility Name

City

Mainz

ZIP/Postal Code

55116

Country

Germany

Facility Name

City

Münster

ZIP/Postal Code

48145

Country

Germany

Facility Name

City

Neuwied

ZIP/Postal Code

56564

Country

Germany

Facility Name

City

Stuttgart

ZIP/Postal Code

70378

Country

Germany

Facility Name

Manati Medical Center

City

Manati

ZIP/Postal Code

00674

Country

Puerto Rico

Facility Name

American Telemedicine Center

City

San Juan

ZIP/Postal Code

00917-3104

Country

Puerto Rico

Facility Name

City

Salford

State/Province

Manchester

ZIP/Postal Code

M6 8HD

Country

United Kingdom

Facility Name

City

Dundee

State/Province

Scotland

ZIP/Postal Code

DD1 9SY

Country

United Kingdom

Facility Name

City

Sheffield

State/Province

South Yorkshire

ZIP/Postal Code

S5 7AU

Country

United Kingdom

Facility Name

City

Ipswich

State/Province

Suffolk

ZIP/Postal Code

IP4 5PD

Country

United Kingdom

Facility Name

City

Manchester

ZIP/Postal Code

M41 5SL

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

IPD Sharing Time Frame

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing URL

https://vivli.org/

Citations:

PubMed Identifier

28671753

Citation

Heller SR, Pratley RE, Sinclair A, Festa A, Kiljanski J, Brusko CS, Duan R, Heine RJ. Glycaemic outcomes of an Individualized treatMent aPproach for oldER vulnerable patIents: A randomized, controlled stUdy in type 2 diabetes Mellitus (IMPERIUM). Diabetes Obes Metab. 2018 Jan;20(1):148-156. doi: 10.1111/dom.13051. Epub 2017 Aug 8.

Results Reference

derived

Learn more about this trial

A Comparison of Two Treatment Strategies in Older Participants With Type 2 Diabetes Mellitus (T2DM)

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