Clinical trial NCT01986881: Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease, The VERTIS CV Study (MK-8835-004)
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2013-11-19
Enrollment: 8246
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The primary hypotheses for the 4 studies are:

1. Overall Cardiovascular Study:

   The time to first occurrence of the composite endpoint of MACE: cardiovascular death, non-fatal myocardial infarction \[MI\] or non-fatal stroke in participants treated with ertugliflozin is non-inferior compared to that in participants treated with placebo.
2. The 3 Glycemic Sub-studies:

   1. The mean reduction from baseline in hemoglobin A1c (A1C) for 15 mg ertugliflozin is greater than that for placebo.
   2. The mean reduction from baseline in A1C for 5 mg ertugliflozin is greater than that for placebo.

Eligibility 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

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.

Primary outcomes:
measure: 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)
timeFrame: Up to approximately 6 years
measure: Baseline Hemoglobin A1C (A1C) (Insulin With or Without Metformin Add-on Glycemic Sub-study)
timeFrame: Baseline
measure: Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Insulin With or Without Metformin Add-on Glycemic Sub-study)
timeFrame: Baseline and Week 18
measure: Baseline Hemoglobin A1C (A1C) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
timeFrame: Baseline
measure: Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
timeFrame: Baseline and Week 18
measure: Baseline Hemoglobin A1C (A1C) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
timeFrame: Baseline
measure: Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
timeFrame: Baseline and Week 18
Secondary outcomes:
measure: Time to Occurrence of Cardiovascular (CV) Death or Hospitalization for Heart Failure (HHF) (On-Study Approach) (Overall Cardiovascular Study)
timeFrame: Up to approximately 6 years
measure: Time to Occurrence of Cardiovascular Death (On-study Approach) (Overall Cardiovascular Study)
timeFrame: Up to approximately 6 years
measure: 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)
timeFrame: Up to approximately 6 years
measure: 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)
timeFrame: Up to approximately 6 years
measure: Time to First Occurrence of Fatal or Non-fatal Myocardial Infarction (On-Study Approach) (Overall Cardiovascular Study)
timeFrame: Up to approximately 6 years
measure: Time to First Occurrence of Fatal or Non-fatal Stroke (FNF Stroke) (On-Study Approach) (Overall Cardiovascular Study)
timeFrame: Up to approximately 6 years
measure: Time to First Occurrence of Hospitalization for Heart Failure (HHF) (On-Study Approach) (Overall Cardiovascular Study)
timeFrame: Up to approximately 6 years
measure: Time to Occurrence of Death From Any Cause (On-Study Approach) (Overall Cardiovascular Study)
timeFrame: Up to approximately 6 years
measure: Andersen-Gill Model for Total MACE (On-Study Approach) (Overall Cardiovascular Study)
timeFrame: Up to approximately 6 years
measure: Andersen-Gill Model for All Cardiovascular Death (CV Death) or Hospitalizations for Heart Failure (HFF) (On-Study Approach) (Overall Cardiovascular Study)
timeFrame: Up to approximately 6 years
measure: Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Overall Cardiovascular Study)
timeFrame: Baseline and Week 18
measure: Change From Baseline in A1C at Week 52 (Overall Cardiovascular Study)
timeFrame: Baseline and Week 52
measure: Change From Baseline in A1C at Month 24 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 24
measure: Change From Baseline in A1C at Month 36 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 36
measure: Change From Baseline in A1C at Month 48 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 48
measure: Change From Baseline in A1C at Month 60 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 60
measure: Change From Baseline in A1C at Month 72 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 72
measure: Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Overall Cardiovascular Study)
timeFrame: Week 18
measure: Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 52 (Overall Cardiovascular Study)
timeFrame: Week 52
measure: Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 24 (Overall Cardiovascular Study)
timeFrame: Month 24
measure: Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 36 (Overall Cardiovascular Study)
timeFrame: Month 36
measure: Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 48 (Overall Cardiovascular Study)
timeFrame: Month 48
measure: Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 60 (Overall Cardiovascular Study)
timeFrame: Month 60
measure: Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Week 18 (Overall Cardiovascular Study)
timeFrame: Week 18
measure: Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Week 52 (Overall Cardiovascular Study)
timeFrame: Week 52
measure: Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 24 (Overall Cardiovascular Study)
timeFrame: Month 24
measure: Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 36 (Overall Cardiovascular Study)
timeFrame: Month 36
measure: Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 48 (Overall Cardiovascular Study)
timeFrame: Month 48
measure: Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 60 (Overall Cardiovascular Study)
timeFrame: Month 60
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)
timeFrame: Baseline and Week 18
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 (Overall Cardiovascular Study)
timeFrame: Baseline and Week 52
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Month 24 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 24
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Month 36 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 36
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Month 48 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 48
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Month 60 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 60
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Month 72 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 72
measure: Time to the First Occurrence of a Participant Receiving Glycemic Rescue Therapy Through Week 18 (Overall Cardiovascular Study)
timeFrame: Up to 18 weeks
measure: Time to Initiation of Insulin for Participants Not on Insulin at Baseline (Overall Cardiovascular Study)
timeFrame: Up to approximately 6 years
measure: Baseline Insulin Dose for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)
timeFrame: Baseline
measure: Change From Baseline in Insulin Dose at Week 18 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)
timeFrame: Baseline and Week 18
measure: Change From Baseline in Insulin Dose at Week 52 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)
timeFrame: Baseline and Week 52
measure: Change From Baseline in Insulin Dose at Month 24 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)
timeFrame: Baseline and Month 24
measure: Change From Baseline in Insulin Dose at Month 36 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)
timeFrame: Baseline and Month 36
measure: Change From Baseline in Insulin Dose at Month 48 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)
timeFrame: Baseline and Month 48
measure: Change From Baseline in Insulin Dose at Month 60 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)
timeFrame: Baseline and Month 60
measure: Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)
timeFrame: Baseline and Week 18
measure: Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 52 (Overall Cardiovascular Study)
timeFrame: Baseline and Week 52
measure: Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 24 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 24
measure: Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 36 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 36
measure: Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 48 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 48
measure: Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 60 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 60
measure: Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 72 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 72
measure: Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)
timeFrame: Baseline and Week 18
measure: Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 52 (Overall Cardiovascular Study)
timeFrame: Baseline and Week 52
measure: Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 24 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 24
measure: Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 36 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 36
measure: Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 48 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 48
measure: Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 60 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 60
measure: Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 72 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 72
measure: Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)
timeFrame: Baseline and Week 18
measure: Change From Baseline in Body Weight at Week 52 (Overall Cardiovascular Study)
timeFrame: Baseline and Week 52
measure: Change From Baseline in Body Weight at Month 24 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 24
measure: Change From Baseline in Body Weight at Month 36 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 36
measure: Change From Baseline in Body Weight at Month 48 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 48
measure: Change From Baseline in Body Weight at Month 60 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 60
measure: Change From Baseline in Body Weight at Month 72 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 72
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 18 (Overall Cardiovascular Study)
timeFrame: Baseline and Week 18
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 (Overall Cardiovascular Study)
timeFrame: Baseline and Week 52
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 24 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 24
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 36 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 36
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 48 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 48
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 60 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 60
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 72 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 72
measure: Baseline Serum Creatinine (Overall Cardiovascular Study)
timeFrame: Baseline
measure: Change From Baseline in Serum Creatinine at Week 18 (Overall Cardiovascular Study)
timeFrame: Baseline and Week 18
measure: Change From Baseline in Serum Creatinine at Week 52 (Overall Cardiovascular Study)
timeFrame: Baseline and Week 52
measure: Change From Baseline in Serum Creatinine at Month 24 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 24
measure: Change From Baseline in Serum Creatinine at Month 36 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 36
measure: Change From Baseline in Serum Creatinine at Month 48 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 48
measure: Change From Baseline in Serum Creatinine at Month 60 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 60
measure: Change From Baseline in Serum Creatinine at Month 72 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 72
measure: Baseline Urinary Albumin/Creatinine Ratio (Overall Cardiovascular Study)
timeFrame: Baseline
measure: Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Week 18 (Overall Cardiovascular Study)
timeFrame: Baseline and Week 18
measure: Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Week 52 (Overall Cardiovascular Study)
timeFrame: Baseline and Week 52
measure: Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 24 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 24
measure: Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 36 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 36
measure: Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 48 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 48
measure: Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 60 (Overall Cardiovascular Study)
timeFrame: Baseline and Month 60
measure: Percentage of Participants With Albuminuria Progression or Regression at Week 18 (Overall Cardiovascular Study)
timeFrame: Week 18
measure: Percentage of Participants With Albuminuria Progression or Regression at Week 52 (Overall Cardiovascular Study)
timeFrame: Week 52
measure: Percentage of Participants With Albuminuria Progression or Regression at Month 24 (Overall Cardiovascular Study)
timeFrame: Month 24
measure: Percentage of Participants With Albuminuria Progression or Regression at Month 36 (Overall Cardiovascular Study)
timeFrame: Month 36
measure: Percentage of Participants With Albuminuria Progression or Regression at Month 48 (Overall Cardiovascular Study)
timeFrame: Month 48
measure: Percentage of Participants With Albuminuria Progression or Regression at Month 60 (Overall Cardiovascular Study)
timeFrame: Month 60
measure: Percentage of Participants Experiencing an Adverse Event (AE) (Overall Cardiovascular Study)
timeFrame: Up to approximately 6 years
measure: Percentage of Participants Experiencing an Adverse Event (AE) (Insulin With or Without Metformin Add-on Glycemic Sub-study)
timeFrame: Up to 18 weeks
measure: Percentage of Participants Experiencing an Adverse Event (AE) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
timeFrame: Up to 18 weeks
measure: Percentage of Participants Experiencing an Adverse Event (AE) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
timeFrame: Up to 18 weeks
measure: Percentage of Participants Discontinuing Study Treatment Due to An AE (Overall Cardiovascular Study)
timeFrame: Up to approximately 6 years
measure: Percentage of Participants Discontinuing Study Treatment Due to An AE (Insulin With or Without Metformin Add-on Glycemic Sub-study)
timeFrame: Up to 18 weeks
measure: Percentage of Participants Discontinuing Study Treatment Due to An AE (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
timeFrame: Up to 18 weeks
measure: Percentage of Participants Discontinuing Study Treatment Due to An AE (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
timeFrame: Up to 18 weeks
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)
timeFrame: Baseline and Week 18
measure: Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)
timeFrame: Baseline and Week 18
measure: 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)
timeFrame: Week 18
measure: 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)
timeFrame: Baseline and Week 18
measure: 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)
timeFrame: Baseline and Week 18
measure: Baseline Insulin Dose for Participants Receiving Insulin at Baseline - (Insulin With or Without Metformin Add-on Glycemic Sub-study)
timeFrame: Baseline
measure: 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)
timeFrame: Baseline and Week 18
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
timeFrame: Baseline and Week 18
measure: Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
timeFrame: Baseline and Week 18
measure: Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
timeFrame: Week 18
measure: Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
timeFrame: Baseline and Week 18
measure: Change From Baseline in Sitting Diastolic Blood (DBP) Pressure at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
timeFrame: Baseline and Week 18
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
timeFrame: Baseline and Week 18
measure: Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
timeFrame: Baseline and Week 18
measure: Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
timeFrame: Week 18
measure: Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
timeFrame: Baseline and Week 18
measure: Change From Baseline in Sitting Diastolic Blood (DBP) Pressure at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
timeFrame: Baseline and Week 18
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.