Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cardiovascular and Renal Microvascular Outcome Study With Linagliptin in Patients With Type 2 Diabetes Mellitus (CARMELINA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01897532
Recruitment Status : Completed
First Posted : July 12, 2013
Results First Posted : January 25, 2019
Last Update Posted : April 4, 2019
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE July 9, 2013
First Posted Date  ICMJE July 12, 2013
Results First Submitted Date  ICMJE December 21, 2018
Results First Posted Date  ICMJE January 25, 2019
Last Update Posted Date April 4, 2019
Actual Study Start Date  ICMJE July 10, 2013
Actual Primary Completion Date January 18, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 21, 2018)
Time to the First Occurrence of Any of the Following Adjudication-confirmed Components of the Primary Composite Endpoint 3-point Major Adverse Cardiovascular (CV) Events (3-point MACE): CV Death, Non-fatal Myocardial Infarction (MI) or Non-fatal Stroke. [ Time Frame: From randomization to individual end of observation; up to 4.3 years ]
Time to event analysis of patients with first occurrence of any of the following adjudication-confirmed components of the primary composite endpoint (3-point MACE): CV death, non-fatal MI or non-fatal stroke. The percentage of observed patients with first occurrence of any of the following adjudication-confirmed components of the primary composite endpoint (3-point MACE) was reported.
Original Primary Outcome Measures  ICMJE
 (submitted: July 9, 2013)
Time to the first occurence of any of the following adjudicated components of the primary composite endpoint (4-point MACE): CV death, non-fatal MI, non fatal stroke and hospitalization for unstable angina pectoris [ Time Frame: 48 months ]
Change History Complete list of historical versions of study NCT01897532 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2018)
Time to the First Occurrence of Any of the Following Adjudication-confirmed Components: Renal Death, Sustained End Stage Renal Disease (ESRD), or Sustained Decrease of 40% or More in Estimated Glomerular Filtration Rate (eGFR). [ Time Frame: From randomization to individual end of observation; up to 4.3 years ]
Time to the first occurrence of any of the following adjudication-confirmed components: renal death, sustained ESRD, or sustained decrease of 40% or more in eGFR. The percentage of observed patients with first occurrence of any of the following adjudication-confirmed components: renal death, sustained ESRD, or sustained decrease of 40% or more in eGFR was reported.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2013)
  • Time to first occurance of any of the following adjudicated components: CV death, non fatal MI and non fatal stroke (3-point MACE) [ Time Frame: 48 months ]
  • Time to first occurance of any of the following adjudicated composite renal endpoint: renal death, end stage renal disease and a sustained decrease of 50% or more in eGFR [ Time Frame: 48 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cardiovascular and Renal Microvascular Outcome Study With Linagliptin in Patients With Type 2 Diabetes Mellitus (CARMELINA)
Official Title  ICMJE CARMELINA: A Multicenter, International, Randomized, Parallel Group, Double-blind, Placebo-controlled, Cardiovascular Safety and Renal Microvascular Outcome Study With Linagliptin, 5 mg Once Daily in Patients With Type 2 Diabetes Mellitus at High Vascular Risk
Brief Summary The aim of the study is to investigate the longterm impact on cardiovascular morbidity, mortality and renal function of treatment with linagliptin in a selected population of patients with Type 2 diabetes mellitus (T2DM) and to compare outcomes against placebo, on a background of standard of care.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Diabetes Mellitus, Type 2
Intervention  ICMJE
  • Drug: Placebo
    placebo matching tablets
  • Drug: Linagliptin
Study Arms  ICMJE
  • Experimental: Linagliptin
    Intervention: Drug: Linagliptin
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 21, 2018)
6991
Original Estimated Enrollment  ICMJE
 (submitted: July 9, 2013)
8300
Actual Study Completion Date  ICMJE January 18, 2018
Actual Primary Completion Date January 18, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  1. Documented diagnosis of T2DM before visit 1(screening).
  2. Male or female patients who are drug-naïve or pre-treated with any antidiabetic background medication, excluding treatment with Glucagon-like Peptide 1 (GLP-1) receptor agonists, Dipeptidyl-peptidase 4 (DPP-4) inhibitors or Sodium Glucose Linked Transporter 2 (SGLT-2) inhibitors if => consecutive 7 days.
  3. Stable antidiabetic background medication (unchanged daily dose) for at least 8 weeks prior to randomization. If insulin is part of the background therapy, the average daily insulin dose should not have changed by more than 10% within the 8 weeks prior to randomization compared with the daily insulin dose at randomization.
  4. HbA1c of => 6.5% and <= 10.0% at Visit 1 (screening)
  5. Age => 18 years at Visit 1(screening). For Japan only: Age => 20 years at Visit 1
  6. Body Mass Index (BMI) <= 45 kg/m2 at Visit 1 (screening)
  7. Signed and dated written informed consent by date of Visit 1(screening) in accordance with Good Clinical Practice (GCP) and local legislation prior to any study related procedure
  8. High risk of cardiovascular (CV) events defined by: 1) albuminuria (micro or macro) and previous macrovascular disease and/or 2) impaired renal function with predefined Urine Albumin Creatinine Ratio (UACR)

Exclusion criteria:

  1. Type 1 diabetes mellitus.
  2. Treatment (=> 7 consecutive days) with GLP-1 receptor agonists, other DPP-4 inhibitors or SGLT-2 inhibitors prior to informed consent. Note: This also includes clinical trials where these antidiabetic drugs have been provided to the patient.
  3. Active liver disease or impaired hepatic function, defined by serum levels of either Alanine Transaminase (ALT) (SGPT), Aspartate transaminase (AST) (SGOT), or alkaline phosphatase (AP) => 3 x upper limit of normal (ULN) as determined at Visit 1.
  4. Estimated Glomerular filtration Rate (eGFR) <15 ml/min/1.73 m2 (severe renal impairment or End Stage Renal Disease (ESRD), Modification of Diet in Renal Disease (MDRD) formula), as determined during screening at Visit 1 and/or the need for maintenance dialysis.
  5. Any previous (or planned within next 12 months) bariatric surgery (open or laparoscopic) or intervention (gastric sleeve).
  6. Pre-planned coronary artery re-vascularisation (PCI, CABG) or any previous PCI and/or CABG <= 2 months prior informed consent.
  7. Known hypersensitivity or allergy to the investigational products or its excipients.
  8. Any previous or current alcohol or drug abuse that would interfere with trial participation in the opinion of the investigator.
  9. Participation in another trial with an investigational drug ongoing or within 2 months prior to visit 1 (screening).
  10. Pre-menopausal women (last menstruation = 1 year prior to informed consent) who are nursing or pregnant, are of child-bearing potential and are not practicing an acceptable method of birth control (acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence (if allowed by local authorities), double barrier method and vasectomised partner) or do not plan to continue using acceptable method of birth control throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial.
  11. Patients considered unreliable by the investigator concerning the requirements for follow up during the study and/or compliance with study drug administration, have a life expectancy less than 5 years for non-CV causes, or have cancer other than non-melanoma skin cancer within last 3 years, or has any other condition than mentioned which in the opinion of the investigator, would not allow safe participation in the study.
  12. Acute coronary syndrome (ACS), diagnosed <= 2 months prior to visit 1 (screening).
  13. Stroke or Transient Ischemic Attack (TIA) <= 3 months prior to visit 1 (screening).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Chile,   Russian Federation,   Argentina,   Brazil,   Bulgaria,   Canada,   China,   Colombia,   Croatia,   Czechia,   Germany,   Hungary,   Israel,   Japan,   Korea, Republic of,   Malaysia,   Mexico,   Netherlands,   Poland,   Portugal,   Romania,   South Africa,   Spain,   Taiwan,   Ukraine,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01897532
Other Study ID Numbers  ICMJE 1218.22
2011-004148-23 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Eli Lilly and Company
Investigators  ICMJE
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account Boehringer Ingelheim
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP