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Stratified Treatment to Ameliorate Diastolic Left Ventricular Stiffness in Heart Failure With Preserved Ejection Fraction (STADIA-HFpEF)

Primary Purpose

Heart Failure, Diastolic

Status
Unknown status
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Dapagliflozin
Placebo
Sponsored by
Mariëlle Scheffer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure, Diastolic

Eligibility Criteria

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

Inclusion Criteria:

  1. Age ≥ 18 years at time of screening
  2. Symptomatic chronic heart failure patients with diagnosis of heart failure and:

    • NYHA class II-IV
    • Preserved systolic Left Ventricular (LV) function, defined by: LV Ejection Fraction (LVEF) ≥ 50% and LV end-diastolic volume index <97 ml/m2
    • Evidence of diastolic LV dysfunction and at least 1 out of the 5 following additional criteria:

      1. H2FPEF score ≥ 6;
      2. HFA-PEFF score ≥ 5;
      3. Pulmonary capillary wedge pressure > 15 mmHg at rest or > 25 mmHg with exercise assessed with right heart catheterization;
  3. Cardiac MRI T1 derived extracellular volume <29% at screening
  4. Oral diuretics, if prescribed to the patient according to local guidelines and at the discretion of the investigator, should be stable for at least 1 week prior to baseline visit
  5. Signed and dated written informed consent in accordance with GCP and local legislation prior to admission to the trial

Exclusion Criteria:

  1. Reduced systolic LV function (LVEF < 50%), measured at any time point in the history of the patient
  2. Obstructive coronary artery disease with evidence of ischemia
  3. Myocardial infarction, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or TIA in past 90 days prior to screening visit
  4. More than mild valve stenosis
  5. More than moderate aortic and/or mitral valve regurgitation
  6. Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. hemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (stress cardiomyopathy), hypertrophic (obstructive) cardiomyopathy or known pericardial constriction
  7. History of mitral valve repair or replacement
  8. Atrial fibrillation or atrial flutter with a resting heart rate > 110 bpm at screening
  9. Acute decompensation that requires intravenous loop diuretics
  10. Systolic blood pressure ≥ 180 mmHg. If SBP > 150 mmHg and < 180 mmHg, the patient should be receiving at least 3 antihypertensive drugs at screening or baseline visit
  11. Symptomatic hypotension and/or a SBP < 100 mmHg at screening or baseline visit
  12. Impaired renal function, defined as eGFR < 30 ml/min/1.73 m2
  13. Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3x upper limit of normal or history of cirrhosis with evidence of portal hypertension
  14. Hemoglobin < 9 g/dl at screening
  15. Chronic obstructive pulmonary disease, more than GOLD class 2
  16. Pulmonary function test with FEV1/FVC < 80%
  17. Primary pulmonary arterial hypertension
  18. Type 1 Diabetes Mellitus
  19. History of ketoacidosis
  20. Any documented active or suspected malignancy or history of malignancy within 2 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix or low risk prostate cancer (biopsy Gleason score of ≤ 6 and clinical stage T1c or T2a)
  21. Current use or prior use of a SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitor within 3 months prior to screening visit. Discontinuation of a SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitor for the purposes of study enrolment is not permitted
  22. Pregnancy or lactation
  23. Any (clinical) condition that, in the investigator's opinion, would jeopardize patients safety while participating in this trial, or may prevent the patient from adhering to the trial protocol

Sites / Locations

  • OLVGRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Group A

Group B

Arm Description

Dapagliflozin - washout period - placebo

Placebo - washout period - Dapagliflozin

Outcomes

Primary Outcome Measures

Left Ventricular (LV) e'
echocardiographically measured
E/e'/LV end-diastolic volume index
echocardiographically measured

Secondary Outcome Measures

Kansas City Cardiomyopathy Questionnaire
6-minute walk test
Left atrial volume
Echocardiographically derived volume
Diastolic parameters
Echocardiographically derived function, filling and compliance of Left Ventricular
Left atrial function
Echocardiographically derived strain analysis, resevoir, conduit and booster pump function

Full Information

First Posted
July 8, 2020
Last Updated
September 18, 2020
Sponsor
Mariëlle Scheffer
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT04475042
Brief Title
Stratified Treatment to Ameliorate Diastolic Left Ventricular Stiffness in Heart Failure With Preserved Ejection Fraction
Acronym
STADIA-HFpEF
Official Title
Stratified Treatment to Ameliorate Diastolic Left Ventricular Stiffness in Heart Failure With Preserved Ejection Fraction. A 35-week, Single-center, Prospective, Double-blind, Controlled, Randomized, 2x2 Crossover, Interventional Phase II Study, Investigating the Effect of Treatment With Dapagliflozin 10mg od on Left Ventricular Distensibility in Patients With Early HFpEF.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Unknown status
Study Start Date
July 1, 2020 (Actual)
Primary Completion Date
November 2021 (Anticipated)
Study Completion Date
May 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Mariëlle Scheffer
Collaborators
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A 35-week, single-center, prospective, double-blind, controlled, randomized, 2x2 crossover, interventional Phase II study, investigating the effect of treatment with dapagliflozin 10mg od on Left Ventricular distensibility in patients with early HFpEF.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
26 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group A
Arm Type
Active Comparator
Arm Description
Dapagliflozin - washout period - placebo
Arm Title
Group B
Arm Type
Active Comparator
Arm Description
Placebo - washout period - Dapagliflozin
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin
Intervention Description
10mg od
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Left Ventricular (LV) e'
Description
echocardiographically measured
Time Frame
13 weeks
Title
E/e'/LV end-diastolic volume index
Description
echocardiographically measured
Time Frame
13 weeks
Secondary Outcome Measure Information:
Title
Kansas City Cardiomyopathy Questionnaire
Time Frame
13 weeks
Title
6-minute walk test
Time Frame
13 weeks
Title
Left atrial volume
Description
Echocardiographically derived volume
Time Frame
13 weeks
Title
Diastolic parameters
Description
Echocardiographically derived function, filling and compliance of Left Ventricular
Time Frame
13 weeks
Title
Left atrial function
Description
Echocardiographically derived strain analysis, resevoir, conduit and booster pump function
Time Frame
13 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years at time of screening Symptomatic chronic heart failure patients with diagnosis of heart failure and: NYHA class II-IV Preserved systolic Left Ventricular (LV) function, defined by: LV Ejection Fraction (LVEF) ≥ 50% and LV end-diastolic volume index <97 ml/m2 Evidence of diastolic LV dysfunction and at least 1 out of the 5 following additional criteria: H2FPEF score ≥ 6; HFA-PEFF score ≥ 5; Pulmonary capillary wedge pressure > 15 mmHg at rest or > 25 mmHg with exercise assessed with right heart catheterization; Cardiac MRI T1 derived extracellular volume <29% at screening Oral diuretics, if prescribed to the patient according to local guidelines and at the discretion of the investigator, should be stable for at least 1 week prior to baseline visit Signed and dated written informed consent in accordance with GCP and local legislation prior to admission to the trial Exclusion Criteria: Reduced systolic LV function (LVEF < 50%), measured at any time point in the history of the patient Obstructive coronary artery disease with evidence of ischemia Myocardial infarction, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or TIA in past 90 days prior to screening visit More than mild valve stenosis More than moderate aortic and/or mitral valve regurgitation Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. hemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (stress cardiomyopathy), hypertrophic (obstructive) cardiomyopathy or known pericardial constriction History of mitral valve repair or replacement Atrial fibrillation or atrial flutter with a resting heart rate > 110 bpm at screening Acute decompensation that requires intravenous loop diuretics Systolic blood pressure ≥ 180 mmHg. If SBP > 150 mmHg and < 180 mmHg, the patient should be receiving at least 3 antihypertensive drugs at screening or baseline visit Symptomatic hypotension and/or a SBP < 100 mmHg at screening or baseline visit Impaired renal function, defined as eGFR < 30 ml/min/1.73 m2 Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3x upper limit of normal or history of cirrhosis with evidence of portal hypertension Hemoglobin < 9 g/dl at screening Chronic obstructive pulmonary disease, more than GOLD class 2 Pulmonary function test with FEV1/FVC < 80% Primary pulmonary arterial hypertension Type 1 Diabetes Mellitus History of ketoacidosis Any documented active or suspected malignancy or history of malignancy within 2 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix or low risk prostate cancer (biopsy Gleason score of ≤ 6 and clinical stage T1c or T2a) Current use or prior use of a SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitor within 3 months prior to screening visit. Discontinuation of a SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitor for the purposes of study enrolment is not permitted Pregnancy or lactation Any (clinical) condition that, in the investigator's opinion, would jeopardize patients safety while participating in this trial, or may prevent the patient from adhering to the trial protocol
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marielle Scheffer, MD
Phone
0031205994889
Email
mailcardio.research@olvg.nl
Facility Information:
Facility Name
OLVG
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1091
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marielle Scheffer
Phone
0031205994889
Email
mailcardio.research@olvg.nl

12. IPD Sharing Statement

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Stratified Treatment to Ameliorate Diastolic Left Ventricular Stiffness in Heart Failure With Preserved Ejection Fraction

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