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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01986881

Registration number

NCT01986881

Ethics application status

Date submitted

12/11/2013

Date registered

19/11/2013

Date last updated

23/09/2022

Titles & IDs

Public title

Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease, The VERTIS CV Study (MK-8835-004)

Scientific title

Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess Cardiovascular Outcomes Following Treatment With Ertugliflozin (MK-8835/PF-04971729) in Subjects With Type 2 Diabetes Mellitus and Established Vascular Disease, The VERTIS CV Study

Secondary ID [1]

2013-002518-11

Secondary ID [2]

8835-004

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Type 2 Diabetes Mellitus

Condition category

Condition code

Cardiovascular

Diseases of the vasculature and circulation including the lymphatic system

Metabolic and Endocrine

Diabetes

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - Ertugliflozin
Treatment: Drugs - Placebo
Treatment: Drugs - Glycemic Rescue

Experimental: Ertugliflozin, 15 mg - Ertugliflozin 15 mg administered orally once daily for up to approximately 6 years

Experimental: Ertugliflozin, 5 mg - Ertugliflozin 5 mg administered orally once daily for up to approximately 6 years

Placebo comparator: Placebo - Matching placebo to ertugliflozin administered orally once daily for up to approximately 6 years

Treatment: Drugs: Ertugliflozin
Oral, once daily, for up to approximately 6 years

Treatment: Drugs: Placebo
Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years

Treatment: Drugs: Glycemic Rescue
Doses of background anti-hyperglycemic agents (AHA), medications will be required to be held constant in all participants enrolled for the initial 18 weeks of the trial with 2 exceptions: First, participant will be prescribed glycemic rescue therapy if they meet specific, progressively more stringent, glycemic thresholds based on repeated, confirmed fasting plasma glucose (FPG) measured at a central laboratory. Second, a participant experiencing clinically significant hypoglycemia according to the investigator at any time during the trial is permitted to have the dose of appropriate background AHA (e.g., insulin, sulfonylurea \[SU\], glinide) reduced or discontinued as per the judgment of the investigator or the treating physician. Choice and dosing of glycemic rescue will be at the discretion of the investigator or the treating physician consistent with standards of care for management of patients with Type 2 diabetes mellitus (T2DM) within the country of the investigational site.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Time to First Occurrence of MACE (Composite Endpoint of Major Adverse Cardiovascular Events [Cardiovascular Death, Non-fatal Myocardial Infarction or Non-fatal Stroke]) (On-Treatment + 365-day Approach) (Overall Cardiovascular Study)

Timepoint [1]

Up to approximately 6 years

Primary outcome [2]

Baseline Hemoglobin A1C (A1C) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Timepoint [2]

Baseline

Primary outcome [3]

Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Timepoint [3]

Baseline and Week 18

Primary outcome [4]

Baseline Hemoglobin A1C (A1C) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Timepoint [4]

Baseline

Primary outcome [5]

Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Timepoint [5]

Baseline and Week 18

Primary outcome [6]

Baseline Hemoglobin A1C (A1C) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Timepoint [6]

Baseline

Primary outcome [7]

Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Timepoint [7]

Baseline and Week 18

Secondary outcome [1]

Time to Occurrence of Cardiovascular (CV) Death or Hospitalization for Heart Failure (HHF) (On-Study Approach) (Overall Cardiovascular Study)

Timepoint [1]

Up to approximately 6 years

Secondary outcome [2]

Time to Occurrence of Cardiovascular Death (On-study Approach) (Overall Cardiovascular Study)

Timepoint [2]

Up to approximately 6 years

Secondary outcome [3]

Time to First Occurrence of the Renal Composite: the Composite of Renal Death, Renal Dialysis/Transplant, or Doubling of Serum Creatinine From Baseline (On-Study Approach) (Overall Cardiovascular Study)

Timepoint [3]

Up to approximately 6 years

Secondary outcome [4]

Time to First Occurrence of MACE Plus (Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke or Hospitalization for Unstable Angina) (On-Study Approach) (Overall Cardiovascular Study)

Timepoint [4]

Up to approximately 6 years

Secondary outcome [5]

Time to First Occurrence of Fatal or Non-fatal Myocardial Infarction (On-Study Approach) (Overall Cardiovascular Study)

Timepoint [5]

Up to approximately 6 years

Secondary outcome [6]

Time to First Occurrence of Fatal or Non-fatal Stroke (FNF Stroke) (On-Study Approach) (Overall Cardiovascular Study)

Timepoint [6]

Up to approximately 6 years

Secondary outcome [7]

Time to First Occurrence of Hospitalization for Heart Failure (HHF) (On-Study Approach) (Overall Cardiovascular Study)

Timepoint [7]

Up to approximately 6 years

Secondary outcome [8]

Time to Occurrence of Death From Any Cause (On-Study Approach) (Overall Cardiovascular Study)

Timepoint [8]

Up to approximately 6 years

Secondary outcome [9]

Andersen-Gill Model for Total MACE (On-Study Approach) (Overall Cardiovascular Study)

Timepoint [9]

Up to approximately 6 years

Secondary outcome [10]

Andersen-Gill Model for All Cardiovascular Death (CV Death) or Hospitalizations for Heart Failure (HFF) (On-Study Approach) (Overall Cardiovascular Study)

Timepoint [10]

Up to approximately 6 years

Secondary outcome [11]

Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Overall Cardiovascular Study)

Timepoint [11]

Baseline and Week 18

Secondary outcome [12]

Change From Baseline in A1C at Week 52 (Overall Cardiovascular Study)

Timepoint [12]

Baseline and Week 52

Secondary outcome [13]

Change From Baseline in A1C at Month 24 (Overall Cardiovascular Study)

Timepoint [13]

Baseline and Month 24

Secondary outcome [14]

Change From Baseline in A1C at Month 36 (Overall Cardiovascular Study)

Timepoint [14]

Baseline and Month 36

Secondary outcome [15]

Change From Baseline in A1C at Month 48 (Overall Cardiovascular Study)

Timepoint [15]

Baseline and Month 48

Secondary outcome [16]

Change From Baseline in A1C at Month 60 (Overall Cardiovascular Study)

Timepoint [16]

Baseline and Month 60

Secondary outcome [17]

Change From Baseline in A1C at Month 72 (Overall Cardiovascular Study)

Timepoint [17]

Baseline and Month 72

Secondary outcome [18]

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Overall Cardiovascular Study)

Timepoint [18]

Week 18

Secondary outcome [19]

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 52 (Overall Cardiovascular Study)

Timepoint [19]

Week 52

Secondary outcome [20]

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 24 (Overall Cardiovascular Study)

Timepoint [20]

Month 24

Secondary outcome [21]

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 36 (Overall Cardiovascular Study)

Timepoint [21]

Month 36

Secondary outcome [22]

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 48 (Overall Cardiovascular Study)

Timepoint [22]

Month 48

Secondary outcome [23]

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 60 (Overall Cardiovascular Study)

Timepoint [23]

Month 60

Secondary outcome [24]

Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Week 18 (Overall Cardiovascular Study)

Timepoint [24]

Week 18

Secondary outcome [25]

Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Week 52 (Overall Cardiovascular Study)

Timepoint [25]

Week 52

Secondary outcome [26]

Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 24 (Overall Cardiovascular Study)

Timepoint [26]

Month 24

Secondary outcome [27]

Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 36 (Overall Cardiovascular Study)

Timepoint [27]

Month 36

Secondary outcome [28]

Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 48 (Overall Cardiovascular Study)

Timepoint [28]

Month 48

Secondary outcome [29]

Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 60 (Overall Cardiovascular Study)

Timepoint [29]

Month 60

Secondary outcome [30]

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)

Timepoint [30]

Baseline and Week 18

Secondary outcome [31]

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 (Overall Cardiovascular Study)

Timepoint [31]

Baseline and Week 52

Secondary outcome [32]

Change From Baseline in Fasting Plasma Glucose (FPG) at Month 24 (Overall Cardiovascular Study)

Timepoint [32]

Baseline and Month 24

Secondary outcome [33]

Change From Baseline in Fasting Plasma Glucose (FPG) at Month 36 (Overall Cardiovascular Study)

Timepoint [33]

Baseline and Month 36

Secondary outcome [34]

Change From Baseline in Fasting Plasma Glucose (FPG) at Month 48 (Overall Cardiovascular Study)

Timepoint [34]

Baseline and Month 48

Secondary outcome [35]

Change From Baseline in Fasting Plasma Glucose (FPG) at Month 60 (Overall Cardiovascular Study)

Timepoint [35]

Baseline and Month 60

Secondary outcome [36]

Change From Baseline in Fasting Plasma Glucose (FPG) at Month 72 (Overall Cardiovascular Study)

Timepoint [36]

Baseline and Month 72

Secondary outcome [37]

Time to the First Occurrence of a Participant Receiving Glycemic Rescue Therapy Through Week 18 (Overall Cardiovascular Study)

Timepoint [37]

Up to 18 weeks

Secondary outcome [38]

Time to Initiation of Insulin for Participants Not on Insulin at Baseline (Overall Cardiovascular Study)

Timepoint [38]

Up to approximately 6 years

Secondary outcome [39]

Baseline Insulin Dose for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

Timepoint [39]

Baseline

Secondary outcome [40]

Change From Baseline in Insulin Dose at Week 18 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

Timepoint [40]

Baseline and Week 18

Secondary outcome [41]

Change From Baseline in Insulin Dose at Week 52 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

Timepoint [41]

Baseline and Week 52

Secondary outcome [42]

Change From Baseline in Insulin Dose at Month 24 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

Timepoint [42]

Baseline and Month 24

Secondary outcome [43]

Change From Baseline in Insulin Dose at Month 36 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

Timepoint [43]

Baseline and Month 36

Secondary outcome [44]

Change From Baseline in Insulin Dose at Month 48 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

Timepoint [44]

Baseline and Month 48

Secondary outcome [45]

Change From Baseline in Insulin Dose at Month 60 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

Timepoint [45]

Baseline and Month 60

Secondary outcome [46]

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)

Timepoint [46]

Baseline and Week 18

Secondary outcome [47]

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 52 (Overall Cardiovascular Study)

Timepoint [47]

Baseline and Week 52

Secondary outcome [48]

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 24 (Overall Cardiovascular Study)

Timepoint [48]

Baseline and Month 24

Secondary outcome [49]

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 36 (Overall Cardiovascular Study)

Timepoint [49]

Baseline and Month 36

Secondary outcome [50]

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 48 (Overall Cardiovascular Study)

Timepoint [50]

Baseline and Month 48

Secondary outcome [51]

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 60 (Overall Cardiovascular Study)

Timepoint [51]

Baseline and Month 60

Secondary outcome [52]

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 72 (Overall Cardiovascular Study)

Timepoint [52]

Baseline and Month 72

Secondary outcome [53]

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)

Timepoint [53]

Baseline and Week 18

Secondary outcome [54]

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 52 (Overall Cardiovascular Study)

Timepoint [54]

Baseline and Week 52

Secondary outcome [55]

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 24 (Overall Cardiovascular Study)

Timepoint [55]

Baseline and Month 24

Secondary outcome [56]

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 36 (Overall Cardiovascular Study)

Timepoint [56]

Baseline and Month 36

Secondary outcome [57]

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 48 (Overall Cardiovascular Study)

Timepoint [57]

Baseline and Month 48

Secondary outcome [58]

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 60 (Overall Cardiovascular Study)

Timepoint [58]

Baseline and Month 60

Secondary outcome [59]

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 72 (Overall Cardiovascular Study)

Timepoint [59]

Baseline and Month 72

Secondary outcome [60]

Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)

Timepoint [60]

Baseline and Week 18

Secondary outcome [61]

Change From Baseline in Body Weight at Week 52 (Overall Cardiovascular Study)

Timepoint [61]

Baseline and Week 52

Secondary outcome [62]

Change From Baseline in Body Weight at Month 24 (Overall Cardiovascular Study)

Timepoint [62]

Baseline and Month 24

Secondary outcome [63]

Change From Baseline in Body Weight at Month 36 (Overall Cardiovascular Study)

Timepoint [63]

Baseline and Month 36

Secondary outcome [64]

Change From Baseline in Body Weight at Month 48 (Overall Cardiovascular Study)

Timepoint [64]

Baseline and Month 48

Secondary outcome [65]

Change From Baseline in Body Weight at Month 60 (Overall Cardiovascular Study)

Timepoint [65]

Baseline and Month 60

Secondary outcome [66]

Change From Baseline in Body Weight at Month 72 (Overall Cardiovascular Study)

Timepoint [66]

Baseline and Month 72

Secondary outcome [67]

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 18 (Overall Cardiovascular Study)

Timepoint [67]

Baseline and Week 18

Secondary outcome [68]

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 (Overall Cardiovascular Study)

Timepoint [68]

Baseline and Week 52

Secondary outcome [69]

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 24 (Overall Cardiovascular Study)

Timepoint [69]

Baseline and Month 24

Secondary outcome [70]

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 36 (Overall Cardiovascular Study)

Timepoint [70]

Baseline and Month 36

Secondary outcome [71]

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 48 (Overall Cardiovascular Study)

Timepoint [71]

Baseline and Month 48

Secondary outcome [72]

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 60 (Overall Cardiovascular Study)

Timepoint [72]

Baseline and Month 60

Secondary outcome [73]

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 72 (Overall Cardiovascular Study)

Timepoint [73]

Baseline and Month 72

Secondary outcome [74]

Baseline Serum Creatinine (Overall Cardiovascular Study)

Timepoint [74]

Baseline

Secondary outcome [75]

Change From Baseline in Serum Creatinine at Week 18 (Overall Cardiovascular Study)

Timepoint [75]

Baseline and Week 18

Secondary outcome [76]

Change From Baseline in Serum Creatinine at Week 52 (Overall Cardiovascular Study)

Timepoint [76]

Baseline and Week 52

Secondary outcome [77]

Change From Baseline in Serum Creatinine at Month 24 (Overall Cardiovascular Study)

Timepoint [77]

Baseline and Month 24

Secondary outcome [78]

Change From Baseline in Serum Creatinine at Month 36 (Overall Cardiovascular Study)

Timepoint [78]

Baseline and Month 36

Secondary outcome [79]

Change From Baseline in Serum Creatinine at Month 48 (Overall Cardiovascular Study)

Timepoint [79]

Baseline and Month 48

Secondary outcome [80]

Change From Baseline in Serum Creatinine at Month 60 (Overall Cardiovascular Study)

Timepoint [80]

Baseline and Month 60

Secondary outcome [81]

Change From Baseline in Serum Creatinine at Month 72 (Overall Cardiovascular Study)

Timepoint [81]

Baseline and Month 72

Secondary outcome [82]

Baseline Urinary Albumin/Creatinine Ratio (Overall Cardiovascular Study)

Timepoint [82]

Baseline

Secondary outcome [83]

Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Week 18 (Overall Cardiovascular Study)

Timepoint [83]

Baseline and Week 18

Secondary outcome [84]

Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Week 52 (Overall Cardiovascular Study)

Timepoint [84]

Baseline and Week 52

Secondary outcome [85]

Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 24 (Overall Cardiovascular Study)

Timepoint [85]

Baseline and Month 24

Secondary outcome [86]

Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 36 (Overall Cardiovascular Study)

Timepoint [86]

Baseline and Month 36

Secondary outcome [87]

Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 48 (Overall Cardiovascular Study)

Timepoint [87]

Baseline and Month 48

Secondary outcome [88]

Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 60 (Overall Cardiovascular Study)

Timepoint [88]

Baseline and Month 60

Secondary outcome [89]

Percentage of Participants With Albuminuria Progression or Regression at Week 18 (Overall Cardiovascular Study)

Timepoint [89]

Week 18

Secondary outcome [90]

Percentage of Participants With Albuminuria Progression or Regression at Week 52 (Overall Cardiovascular Study)

Timepoint [90]

Week 52

Secondary outcome [91]

Percentage of Participants With Albuminuria Progression or Regression at Month 24 (Overall Cardiovascular Study)

Timepoint [91]

Month 24

Secondary outcome [92]

Percentage of Participants With Albuminuria Progression or Regression at Month 36 (Overall Cardiovascular Study)

Timepoint [92]

Month 36

Secondary outcome [93]

Percentage of Participants With Albuminuria Progression or Regression at Month 48 (Overall Cardiovascular Study)

Timepoint [93]

Month 48

Secondary outcome [94]

Percentage of Participants With Albuminuria Progression or Regression at Month 60 (Overall Cardiovascular Study)

Timepoint [94]

Month 60

Secondary outcome [95]

Percentage of Participants Experiencing an Adverse Event (AE) (Overall Cardiovascular Study)

Timepoint [95]

Up to approximately 6 years

Secondary outcome [96]

Percentage of Participants Experiencing an Adverse Event (AE) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Timepoint [96]

Up to 18 weeks

Secondary outcome [97]

Percentage of Participants Experiencing an Adverse Event (AE) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Timepoint [97]

Up to 18 weeks

Secondary outcome [98]

Percentage of Participants Experiencing an Adverse Event (AE) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Timepoint [98]

Up to 18 weeks

Secondary outcome [99]

Percentage of Participants Discontinuing Study Treatment Due to An AE (Overall Cardiovascular Study)

Timepoint [99]

Up to approximately 6 years

Secondary outcome [100]

Percentage of Participants Discontinuing Study Treatment Due to An AE (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Timepoint [100]

Up to 18 weeks

Secondary outcome [101]

Percentage of Participants Discontinuing Study Treatment Due to An AE (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Timepoint [101]

Up to 18 weeks

Secondary outcome [102]

Percentage of Participants Discontinuing Study Treatment Due to An AE (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Timepoint [102]

Up to 18 weeks

Secondary outcome [103]

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Timepoint [103]

Baseline and Week 18

Secondary outcome [104]

Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Timepoint [104]

Baseline and Week 18

Secondary outcome [105]

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Timepoint [105]

Week 18

Secondary outcome [106]

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Timepoint [106]

Baseline and Week 18

Secondary outcome [107]

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Timepoint [107]

Baseline and Week 18

Secondary outcome [108]

Baseline Insulin Dose for Participants Receiving Insulin at Baseline - (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Timepoint [108]

Baseline

Secondary outcome [109]

Change From Baseline at Week 18 in Insulin Dose for Participants Receiving Insulin at Baseline - Including Rescue Approach (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Timepoint [109]

Baseline and Week 18

Secondary outcome [110]

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Timepoint [110]

Baseline and Week 18

Secondary outcome [111]

Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Timepoint [111]

Baseline and Week 18

Secondary outcome [112]

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Timepoint [112]

Week 18

Secondary outcome [113]

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Timepoint [113]

Baseline and Week 18

Secondary outcome [114]

Change From Baseline in Sitting Diastolic Blood (DBP) Pressure at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Timepoint [114]

Baseline and Week 18

Secondary outcome [115]

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Timepoint [115]

Baseline and Week 18

Secondary outcome [116]

Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Timepoint [116]

Baseline and Week 18

Secondary outcome [117]

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Timepoint [117]

Week 18

Secondary outcome [118]

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Timepoint [118]

Baseline and Week 18

Secondary outcome [119]

Change From Baseline in Sitting Diastolic Blood (DBP) Pressure at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Timepoint [119]

Baseline and Week 18

Eligibility

Key inclusion criteria

Inclusion Criteria (Overall Cardiovascular Study):

* Diagnosis of T2DM in accordance with American Diabetes Association (ADA) guidelines
* Hemoglobin A1c (A1C) at the start of study participation of 7.0-10.5% (53-91 mmol/mol)
* On stable allowable anti-hyperglycemic agents (AHA) or on no background AHA for at least 8 weeks prior to the study participation
* Body Mass Index (BMI) > or = to 18.0 kg/m^2
* Evidence or a history of atherosclerosis involving the coronary, cerebral or peripheral vascular systems
* There is adequate documentation of the objective evidence that the participant has established vascular disease such as investigational site's medical records, copies of such records from other institutions, or a letter from a referring physician that specifically states the diagnosis and date of the most recent occurrence of the qualifying event(s) or procedure(s).
* Male, female not or reproductive potential, or female of reproductive potential who agrees to be abstinent from heterosexual activity or agrees to use or have their partner use 2 acceptable methods of contraception

Minimum age

40 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Exclusion Criteria (Overall Cardiovascular Study):

* Previous randomization into this trial
* Experiencing a cardiovascular event (myocardial infarction or stroke) or undergoing coronary angioplasty or peripheral intervention procedure between the Screening Visit and randomization
* Undergoing any cardiovascular surgery (valvular surgery) within 3 months of study participation
* Planned revascularization or peripheral intervention procedure or other cardiovascular surgery
* New York Heart Association (NYHA) IV heart failure at study participation
* History of type 1 diabetes mellitus or a history of ketoacidosis

Key Inclusion Criteria for the 3 Glycemic Sub-studies:

1. Insulin With or Without Metformin Sub-study: Stable doses of insulin (>=20 units/day, with variations up to 10% in the daily dose permitted) with or without metformin (>=1500 mg/day) for at least 8 weeks prior to the time of the Screening Visit (V1) and during the period between the Screening Visit (V1) and randomization.
2. Sulfonylurea (SU) Monotherapy Sub-study: Participants receiving a stable dose of SU monotherapy for at least 8 weeks prior to the time of the Screening Visit (V1) and during the period between the Screening Visit (V1) and randomization.
3. Metformin with SU Sub-study: Participants receiving a stable dose metformin (=1500 mg/day) with a SU for at least 8 weeks prior to the time of the Screening Visit (V1) and during the period between the Screening Visit (V1) and randomization.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

4/11/2013

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

27/12/2019

Sample size

Target

Accrual to date

Final

8246

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

Merck Sharp & Dohme LLC

Address

Country

Other collaborator category [1]

Commercial sector/industry

Name [1]

Pfizer

Address [1]

Country [1]

Ethics approval

Ethics application status

Summary

Brief summary

An overall study of the cardiovascular outcomes following treatment with ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and established vascular disease. The main objective of this study is to assess the cardiovascular safety of ertugliflozin. This trial includes 3 pre-defined glycemic sub-studies; 1. In participants receiving background insulin with or without metformin, 2. In participants receiving background sulfonylurea monotherapy, and 3. In participants receiving background metformin with sulfonylurea (all fully-enrolled).

Participants enrolled prior to Amendment 1 were in the overall study as well as a sub-study, if they met certain entry criteria. Participants enrolled following the start of Amendment 1 were only enrolled in the overall study. The sub-studies were the initial 18 weeks of the overall study period.

Trial website

https://clinicaltrials.gov/study/NCT01986881

Trial related presentations / publications

Cannon CP, McGuire DK, Pratley R, Dagogo-Jack S, Mancuso J, Huyck S, Charbonnel B, Shih WJ, Gallo S, Masiukiewicz U, Golm G, Cosentino F, Lauring B, Terra SG; VERTIS-CV Investigators. Design and baseline characteristics of the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes trial (VERTIS-CV). Am Heart J. 2018 Dec;206:11-23. doi: 10.1016/j.ahj.2018.08.016. Epub 2018 Sep 5.
Segar MW, Kolkailah AA, Frederich R, Pong A, Cannon CP, Cosentino F, Dagogo-Jack S, McGuire DK, Pratley RE, Liu CC, Maldonado M, Liu J, Cater NB, Pandey A, Cherney DZI. Mediators of ertugliflozin effects on heart failure and kidney outcomes among patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2022 Sep;24(9):1829-1839. doi: 10.1111/dom.14769. Epub 2022 Jun 15.
Wojeck BS, Inzucchi SE, Neeland IJ, Mancuso JP, Frederich R, Masiukiewicz U, Cater NB, McGuire DK, Cannon CP, Yaggi HK. Ertugliflozin and incident obstructive sleep apnea: an analysis from the VERTIS CV trial. Sleep Breath. 2023 May;27(2):669-672. doi: 10.1007/s11325-022-02594-2. Epub 2022 May 20.
Dagogo-Jack S, Cannon CP, Cherney DZI, Cosentino F, Liu J, Pong A, Gantz I, Frederich R, Mancuso JP, Pratley RE. Cardiorenal outcomes with ertugliflozin assessed according to baseline glucose-lowering agent: An analysis from VERTIS CV. Diabetes Obes Metab. 2022 Jul;24(7):1245-1254. doi: 10.1111/dom.14691. Epub 2022 Mar 29.
Cherney DZI, Cosentino F, Pratley RE, Dagogo-Jack S, Frederich R, Maldonado M, Liu J, Pong A, Liu CC, Cannon CP; VERTIS CV Investigators. The differential effects of ertugliflozin on glucosuria and natriuresis biomarkers: Prespecified analyses from VERTIS CV. Diabetes Obes Metab. 2022 Jun;24(6):1114-1122. doi: 10.1111/dom.14677. Epub 2022 Mar 28.
Dagogo-Jack S, Pratley RE, Cherney DZI, McGuire DK, Cosentino F, Shih WJ, Liu J, Frederich R, Mancuso JP, Raji A, Gantz I. Glycemic efficacy and safety of the SGLT2 inhibitor ertugliflozin in patients with type 2 diabetes and stage 3 chronic kidney disease: an analysis from the VERTIS CV randomized trial. BMJ Open Diabetes Res Care. 2021 Oct;9(1):e002484. doi: 10.1136/bmjdrc-2021-002484.
Cherney DZI, Cosentino F, Dagogo-Jack S, McGuire DK, Pratley R, Frederich R, Maldonado M, Liu CC, Liu J, Pong A, Cannon CP; VERTIS CV Investigators. Ertugliflozin and Slope of Chronic eGFR: Prespecified Analyses from the Randomized VERTIS CV Trial. Clin J Am Soc Nephrol. 2021 Sep;16(9):1345-1354. doi: 10.2215/CJN.01130121. Epub 2021 Jun 18.
Lingvay I, Greenberg M, Gallo S, Shi H, Liu J, Gantz I. Efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus and established cardiovascular disease using insulin: A VERTIS CV substudy. Diabetes Obes Metab. 2021 Jul;23(7):1640-1651. doi: 10.1111/dom.14385. Epub 2021 May 5.
Budoff MJ, Davis TME, Palmer AG, Frederich R, Lawrence DE, Liu J, Gantz I, Derosa G. Efficacy and Safety of Ertugliflozin in Patients with Type 2 Diabetes Inadequately Controlled by Metformin and Sulfonylurea: A Sub-Study of VERTIS CV. Diabetes Ther. 2021 May;12(5):1279-1297. doi: 10.1007/s13300-021-01033-x. Epub 2021 Mar 15.
Strojek K, Pandey AS, Dell V, Sisson M, Wang S, Huyck S, Liu J, Gantz I. Efficacy and Safety of Ertugliflozin in Patients With Diabetes Mellitus Inadequately Controlled by Sulfonylurea Monotherapy: a Substudy of VERTIS CV. Diabetes Ther. 2021 Apr;12(4):1175-1192. doi: 10.1007/s13300-021-01018-w. Epub 2021 Mar 10.
Cherney DZI, Charbonnel B, Cosentino F, Dagogo-Jack S, McGuire DK, Pratley R, Shih WJ, Frederich R, Maldonado M, Pong A, Cannon CP; VERTIS CV Investigators. Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial. Diabetologia. 2021 Jun;64(6):1256-1267. doi: 10.1007/s00125-021-05407-5. Epub 2021 Mar 4.
Cosentino F, Cannon CP, Cherney DZI, Masiukiewicz U, Pratley R, Dagogo-Jack S, Frederich R, Charbonnel B, Mancuso J, Shih WJ, Terra SG, Cater NB, Gantz I, McGuire DK; VERTIS CV Investigators. Efficacy of Ertugliflozin on Heart Failure-Related Events in Patients With Type 2 Diabetes Mellitus and Established Atherosclerotic Cardiovascular Disease: Results of the VERTIS CV Trial. Circulation. 2020 Dec 8;142(23):2205-2215. doi: 10.1161/CIRCULATIONAHA.120.050255. Epub 2020 Oct 7.
Cannon CP, Pratley R, Dagogo-Jack S, Mancuso J, Huyck S, Masiukiewicz U, Charbonnel B, Frederich R, Gallo S, Cosentino F, Shih WJ, Gantz I, Terra SG, Cherney DZI, McGuire DK; VERTIS CV Investigators. Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. N Engl J Med. 2020 Oct 8;383(15):1425-1435. doi: 10.1056/NEJMoa2004967. Epub 2020 Sep 23.
Wittbrodt ET, Eudicone JM, Bell KF, Enhoffer DM, Latham K, Green JB. Eligibility varies among the 4 sodium-glucose cotransporter-2 inhibitor cardiovascular outcomes trials: implications for the general type 2 diabetes US population. Am J Manag Care. 2018 Apr;24(8 Suppl):S138-S145.

Public notes

This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts

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Medical Director

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Merck Sharp & Dohme LLC

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Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01986881

Trial Review

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For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01986881