Back to resultsErtugliflozin in Chronic Heart Failure
Primary Purpose
Heart Failure
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ertugliflozin
Metolazone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring Ertugliflozin, Metolazone
Eligibility Criteria
Inclusion Criteria:
- A clinical diagnosis of ADHF with at least one objective sign of volume overload (rales, edema, elevated JVP, or preadmission weight gain)
- As judged by the treating physician, a projected need and ability to tolerate treatment with an extended need for IV diuretics with the goal of significant fluid removal (i.e., goal >1L/day net fluid loss)
- Chronic daily oral loop diuretic dose > or equal to 20mg furosemide equivalents for at least one month prior to admission
- eGFR 30 mL/min/1.73 m2
- Signed informed consent
Exclusion Criteria:
- Current use or plan to initiate renal replacement therapy or ultrafiltration this hospital admission
- Significant bladder dysfunction or urinary incontinence
- Inability to comply with the serial urine collection procedures
- Current use of a thiazide or thiazide like diuretics or use within 5 half-lives of the drug, including metolazone
- Prior heart transplant, critical stenotic valvular disease or complex congenital heart
- History of type 1 diabetes, diabetic ketoacidosis, "brittle" diabetes or frequent hypoglycemia or severe hypoglycemic episodes requiring emergent intervention (ER visit or EMS response, glucagon administration or forced oral carbs) in the last 3 months
- History of or current urosepsis or frequent urinary tract infections
- Anemia with hemoglobin <8g/dL (due to required phlebotomy for the study)
- Pregnancy or breastfeeding
Sites / Locations
- Yale School of MedicineRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Ertugliflozin
Metolazone
Placebo
Arm Description
Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo
Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo
Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo
Outcomes
Primary Outcome Measures
Natriuretic effect of adjuvant to loop diuretic therapy
The natriuretic effect (urine sodium concentration) of each arm with loop diuretic therapy will be measured by the urine sodium output.
Change from baseline to day 7 of total body water by add-on to loop diuretic therapy (Chronic)
The primary outcome of the chronic effects of add-on placebo, thiazide-like diuretic, or SGLT2 inhibitor is to determine the change in total body water from baseline to day 7
Change from baseline to 6 weeks total body water by add-on to loop diuretic therapy (Chronic)
The primary outcome of the chronic effects of add-on placebo, thiazide-like diuretic, or SGLT2 inhibitor is to determine the change in total body water from baseline to 6 weeks.
Secondary Outcome Measures
Full Information
NCT ID
NCT04438213
First Posted
June 3, 2020
Last Updated
February 17, 2023
Sponsor
Yale University
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT04438213
Brief Title
Ertugliflozin in Chronic Heart Failure
Official Title
Ertugliflozin in Chronic Heart Failure: Cardio-renal and Diuretic Effects
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 10, 2021 (Actual)
Primary Completion Date
January 31, 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine the effects on heart failure signs and symptoms of the use of either ertugliflozin, metolazone or placebo, in conjunction with intravenous loop diuretic use in acute settings and chronic oral loop diuretic therapy.
There are two general purposes for this study. The proposed study is both larger and more rigorous than essentially all PK/PD studies that form the basis of current practice with loop diuretics as well as all studies looking at add-on thiazide therapy (current guideline-recommended adjuvant). The second is to generate a mechanistic understanding of the pleotropic cardio-renal factors with chronic therapy that differentiate ertugliflozin from traditional diuretics particularly in how they maintain reduced blood volume without the complication of over-diuresis and volume depletion.
Detailed Description
This is a randomized placebo controlled mechanistic study to understand the utility of ertugliflozin in acute and post-acute hospitalized heart failure patients with or without diabetes, compared to both placebo and the active control metolazone. The broad study design will be designed around evaluation of change in gold standard determined body fluid spaces (blood volume, extracellular fluid, total body water), administering a sodium chloride challenge, and collecting the necessary biospecimens to test our hypotheses. The general study design will randomize to ertugliflozin vs. placebo early during IV diuretic therapy with continuation post discharge for a total therapy of 6 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Ertugliflozin, Metolazone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ertugliflozin
Arm Type
Experimental
Arm Description
Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo
Arm Title
Metolazone
Arm Type
Experimental
Arm Description
Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo
Intervention Type
Drug
Intervention Name(s)
Ertugliflozin
Intervention Description
Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo
Intervention Type
Drug
Intervention Name(s)
Metolazone
Intervention Description
Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo
Primary Outcome Measure Information:
Title
Natriuretic effect of adjuvant to loop diuretic therapy
Description
The natriuretic effect (urine sodium concentration) of each arm with loop diuretic therapy will be measured by the urine sodium output.
Time Frame
1 day
Title
Change from baseline to day 7 of total body water by add-on to loop diuretic therapy (Chronic)
Description
The primary outcome of the chronic effects of add-on placebo, thiazide-like diuretic, or SGLT2 inhibitor is to determine the change in total body water from baseline to day 7
Time Frame
7 days
Title
Change from baseline to 6 weeks total body water by add-on to loop diuretic therapy (Chronic)
Description
The primary outcome of the chronic effects of add-on placebo, thiazide-like diuretic, or SGLT2 inhibitor is to determine the change in total body water from baseline to 6 weeks.
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
A clinical diagnosis of ADHF with at least one objective sign of volume overload (rales, edema, elevated JVP, or preadmission weight gain)
As judged by the treating physician, a projected need and ability to tolerate treatment with an extended need for IV diuretics with the goal of significant fluid removal (i.e., goal >1L/day net fluid loss)
Chronic daily oral loop diuretic dose > or equal to 20mg furosemide equivalents for at least one month prior to admission
eGFR 30 mL/min/1.73 m2
Signed informed consent
Exclusion Criteria:
Current use or plan to initiate renal replacement therapy or ultrafiltration this hospital admission
Significant bladder dysfunction or urinary incontinence
Inability to comply with the serial urine collection procedures
Current use of a thiazide or thiazide like diuretics or use within 5 half-lives of the drug, including metolazone
Prior heart transplant, critical stenotic valvular disease or complex congenital heart
History of type 1 diabetes, diabetic ketoacidosis, "brittle" diabetes or frequent hypoglycemia or severe hypoglycemic episodes requiring emergent intervention (ER visit or EMS response, glucagon administration or forced oral carbs) in the last 3 months
History of or current urosepsis or frequent urinary tract infections
Anemia with hemoglobin <8g/dL (due to required phlebotomy for the study)
Pregnancy or breastfeeding
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Katherine Keith, RN
Phone
(203) 737-3571
Email
katherine.keith@yale.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Veena Rao, PhD
Phone
(203) 785-7917
Email
veena.s.rao@yale.edu
Facility Information:
Facility Name
Yale School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeffrey Testani, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Ertugliflozin in Chronic Heart Failure
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