This Will be a Randomized Comparison of the Proteomic Effects of Vicadrostat/Empagliflozin Versus Empagliflozin and Versus Empagliflozin/Spironolactone in Heart Failure Patients With Preserved Ejection Fraction (SPECTRA-HFpEF)
A Randomized Comparison of the Proteomic Effects of Vicadrostat/Empagliflozin Versus Empagliflozin and Versus Empagliflozin/Spironolactone in Heart Failure Patients With Preserved Ejection Fraction
The SPECTRA-HFpEF Study is a randomized, double-blind, Phase 2 clinical study designed to evaluate and compare the biological effects of vicadrostat in combination with empagliflozin, empagliflozin alone, and spironolactone in combination with empagliflozin in adults with heart failure and preserved ejection fraction. The study will enroll approximately 200 participants with chronic heart failure, New York Heart Association Class II to IV symptoms, and left ventricular ejection fraction greater than 40%. The primary objective is to determine whether treatment with vicadrostat/empagliflozin produces differential changes in circulating plasma proteins compared with spironolactone/empagliflozin, using a broad proteomic panel measured over the course of treatment. These proteomic changes may help identify biological pathways affected by each treatment strategy, including pathways related to inflammation, myocardial fibrosis and remodeling, kidney function, cardiac stress, and aldosterone-related signaling.
Participants will complete an approximately 26-week study period, including screening, treatment, and follow-up phases. After screening and any required washout of prior sodium-glucose cotransporter 2 inhibitor therapy, participants will receive open-label empagliflozin and will be randomized in a blinded manner to receive vicadrostat or placebo during the first treatment period. During the second treatment period, participants will receive either continued vicadrostat with empagliflozin or spironolactone with empagliflozin. During the third treatment period, vicadrostat or spironolactone will be discontinued while empagliflozin is continued. Blood and urine samples will be collected at specified visits to evaluate changes in proteomic markers, renin-angiotensin-aldosterone system biomarkers, collagen turnover markers, sex hormone markers, kidney function, proteinuria, inflammatory biomarkers, and cardiac stress biomarkers. Echocardiography and patient-reported health status assessments will also be performed to explore potential effects on cardiac structure, function, symptoms, and quality of life.
The study is intended to improve understanding of how aldosterone synthase inhibition with vicadrostat differs from mineralocorticoid receptor antagonism with spironolactone when each is used with empagliflozin in patients with heart failure and preserved ejection fraction. By comparing treatment-related proteomic and biomarker changes across study arms, the study may provide insight into mechanistic differences between these therapeutic approaches and help inform future development of targeted combination therapies for heart failure. Safety and tolerability will be monitored throughout the study through collection of adverse events, serious adverse events, vital signs, electrocardiograms, physical examinations, and clinical laboratory assessments, including kidney function and serum potassium monitoring.
Přehled studie
Postavení
Intervence / Léčba
Detailní popis
This double-blind, randomized, Phase 2 study is being conducted in adult participants with heart failure (HF) and left ventricular ejection fraction (LVEF) >40% to primarily assess the impact of vicadrostat/empagliflozin (vica/empa) versus placebo/empa and versus spironolactone (spiro)/empa on the proteome.
The study includes 4 discrete study periods. All doses will be given once daily (QD) during the Treatment Periods. Empa will be given open-label.
-
Screening: 4 week duration including a 2-week washout period of SGLT2 inhibitors
-
Treatment Period 1: participants will be given open-label empa 10 mg QD and randomized to vica 10 mg QD versus placebo QD (8 weeks)
-
Treatment Period 2: vica 10 mg QD/empa 10 mg QD versus spiro 25-50 mg QD/empa 10 mg QD (10 weeks)
- Participants randomized to vica in Treatment Period 1 will continue treatment and remain blinded.
- Participants randomized to placebo in Treatment Period 1 will be given blinded spiro/empa.
-
Treatment Period 3:
- Discontinuation of vica or spiro.
- Continuation of open-label empa in both treatment arms.
The main questions for the analysis include:
- The relative change in plasma concentration of a pre-specified panel of 5400 proteins measured using the Olink Explore HT panel from Study Visit 1 (baseline) through Study Visit 7 (18 weeks), compared between those treated with vica/empa versus spiro/empa
- The safety profile of using Incidence of TEAEs and SAEs and change from baseline in clinical laboratory values, vital signs, and ECGs.
- Additional protenomic analyses between the groups
- Other blood markers/biomarkers
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 2
Kontakty a umístění
Studijní kontakt
- Jméno: Patricia M Wedge, Chief Operating Officer, RN, BSN
- Telefonní číslo: 6173075320
- E-mail: patricia.wedge@baiminstitute.org
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
-
Participant is aged ≥18 years.
-
Participant provides informed consent to participate in the study in accordance with ICH-GCP and local legislation prior to any study procedures taking place.
-
Women of childbearing potential (WOCBP) must agree to use a highly effective method of birth control per ICH M3 (R2) that results in a low failure rate of <1% per year when used consistently and correctly.
-
Participant has chronic HF diagnosed ≥3 months before enrollment, and in New York Heart Association (NYHA) class II-IV.
-
Participant has LVEF >40% in the 12 months prior to enrollment.
-
N-terminal pro-B type natriuretic peptide (NT-proBNP) must be:
NT-proBNP level (kg/m²) BMI <27 (kg/m²) BMI ≥27 to <35 BMI ≥35 Without AF or AFL Non-Black participants ≥300 pg/mL ≥200 pg/mL ≥125 pg/mL Black Participants ≥240 pg/mL ≥160 pg/mL ≥100 pg/mL With AF or AFL Non-Black participants ≥600 pg/mL ≥400 pg/mL ≥250 pg/mL Black Participants ≥480 pg/mL ≥320 pg/mL ≥200 pg/mL Abbreviations: AF: atrial fibrillation; AFL: atrial flutter. Note: Race is self-reported.
-
Participants must have ≥1 of the following:
-
Currently treated with diuretic therapy (e.g. loop diuretics or thiazides) and on a stable dose for ≥1 week prior to enrollment.
-
Currently treated with an SGLT2 inhibitor and on a stable dose for at ≥1 week prior to enrollment; those receiving an SGLT2 inhibitor for treatment of diabetes mellitus will be monitored for need of extra glucose lowering treatment by the study investigator in conjunction with the local physician during the washout period per usual care.
-
Documented hospitalization for HF within 6 months prior to enrollment.
-
Elevated cardiac filling pressures (e.g. pulmonary capillary wedge pressure ≥15 mm at rest or ≥25 mm with exercise) within 6 months prior to enrollment.
-
Markedly elevated NT-proBNP
- In participants without AF/AFL: ≥900 pg/mL
- In participants with AF/AFL: ≥1800 pg/mL
-
UACR ≥30 mg/g.
-
At least 2 echocardiographic cardiac structural changes from the following:
- Left ventricular hypertrophy
- E/e' ≥9
- Left atrial volume index >33 mL/m2
-
Exclusion Criteria:
-
Treatment with an MRA (e.g. spironolactone, eplerenone, finerenone) within 14 days prior to enrollment and no intention to initiate MRA during the study.
-
Treatment with amiloride, direct renin inhibitor (e.g. aliskiren), or the combination of ACEi plus ARB.
-
Treatment with any other ASi.
-
Major contraindication to SGLT2 inhibition, including history of Type 1 diabetes or previous ketoacidosis.
-
eGFR < 20 mL/min/1.73m2 at screening.
-
Serum potassium >5.2 mmol/L at screening.
-
Myocardial infarction, cerebrovascular accident, transient ischemic attack, stroke, coronary artery bypass graft (CABG) surgery, heart valve surgery or any other major surgery (per investigator judgement) within 90 days prior to enrollment, or scheduled for major elective surgery (e.g. hip replacement, CABG surgery).
-
Heart transplant recipient, awaiting heart transplant, or currently implanted left ventricular assist device.
-
Known cardiomyopathy due to infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, hypertrophic obstructive cardiomyopathy, or known pericardial constriction, or cardiomyopathy with potentially reversible cause such as stress or peripartum cardiomyopathy or cardiomyopathy induced by chemotherapy within the 12 months prior to enrollment.
-
Acute inflammatory heart disease, such as acute myocarditis, within the 90 days preceding enrollment.
-
Known severe valvular heart disease (obstructive or regurgitant), per investigator judgment, or valvular heart disease scheduled for surgical or invasive procedures at enrollment, or anticipated invasive treatment during the study.
-
Active or prior cancer of any kind except for non-melanoma skin cancers.
-
Psychiatric illness, cognitive impairment, behavioral issues, or social situation that in the opinion of the investigator will compromise the participant's ability to comply with study procedures
-
Participant is pregnant or lactating or plans to become pregnant during the study or up to 2 weeks after the study.
-
Patient has a known hypersensitivity to any components of the IMPs or any of their excipients that, in the opinion of the investigator, suggests a high risk for a severe hypersensitivity reaction while on treatment.
-
Any other condition not specified above that in the opinion of the investigator would confound the interpretation of data from the study
-
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: empa plus vica
Participants randomized to this arm will receive Vica 10 mg and empa 10 mg (in treatment periods 1 and 2) with empa 10 mg (treatment period 3) |
Participants will be randomized to to this arm will receive empa (open-label)/vica (blinded). In treatment period 1 those randomized to empa/vica will be administered one tablet of empa 10 mg QD and one tablet of vica 10 mg QD for 8 weeks. In treatment period 2 for those randomized to empa/vica will continue to take empa 10 mg QD and vica 10 mg QD plus a placebo-matching spiro for 10 weeks. In treatment period 3, this group will receive open-label empa 10 mg QD for 4 weeks. |
|
Aktivní komparátor: empa plus spironolactone
Participants randomized to this arm will receive empa 10 mg QD and vica matching placebo tablet in treatment period 1; empa 10 mg QD plus spironolactone 25 mg titrating to 50 mg QD in treatment period 2 and empa 10 mg in treatment period 3. |
For those randomized to empa (open-label) spiro (blinded), in treatment period 1 they will be administered one tablet of empa 10 mg QD and vica matching placebo for 8 weeks. In treatment period 2 for those randomized to empa/spiro, they will take empa 10 mg QD, spiro 25 mg titrating to 50 mg QD plus a vica matching placebo tablet for 10 weeks. In treatment period 3, this group will receive open-label empa 10 mg QD for 4 weeks. |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Differences in the proteomic regulation following Treatment Period 2
Časové okno: 18 weeks
|
To evaluate the relative change in plasma concentration of a pre-specified panel of 5400 proteins measured using the Olink Explore HT panel from Study Visit 1 (baseline) through Study Visit 7 (18 weeks), compared between those treated with vica/empa versus spiro/empa. |
18 weeks
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Differences in the proteomic regulation following Treatment Period 1.
Časové okno: 8 weeks
|
To evaluate the relative change in plasma concentration of a pre-specified panel of 5400 proteins measured using the Olink Explore HT panel from Study Visit 1 (baseline) through Study Visit 4 (8 weeks), compared between those treated with vica/empa versus empa will be evaluated. |
8 weeks
|
|
Differences in the proteomic regulation following Treatment Period 2
Časové okno: 10 Weeks (8 weeks through 18 weeks)
|
To evaluate the relative change in plasma concentration of a pre-specified panel of 5400 proteins measured using the Olink Explore HT panel from Visit 4 (8 weeks) through Study 7 (18 weeks), compared between those treated with vica/empa versus empa. |
10 Weeks (8 weeks through 18 weeks)
|
|
Differences in proteomic regulation following Treatment Period 3.
Časové okno: 4 weeks
|
To compare the relative change in plasma concentration of a pre-specified panel of 5400 proteins measured using the Olink Explore HT panel from Study Visit 7 (18 weeks) through Study Visit 8 (22 weeks), compared between those treated with vica/empa in Treatment Periods 1 and 3 versus empa alone in Treatment Period 3. |
4 weeks
|
|
Differences in renin, aldosterone and aldosterone precursors across each Treatment Period.
Časové okno: 22 weeks
|
To evaluate mean within- participant change in plasma renin activity/concentration, serum aldosterone, and 11-deoxycorticosterone from the beginning and end of each Treatment Period, compared across treatment arms. |
22 weeks
|
|
Differences in markers of collagen synthesis, degradation and cross-linking across each Treatment Period.
Časové okno: 22 weeks
|
To evaluate mean within- participant change in plasma PICP, CITP, MMP1, PIIINP, and Pro-C6 from the beginning and end of each Treatment Period, compared across treatment arms. |
22 weeks
|
|
Differences in plasma progesterone across each Treatment Period.
Časové okno: 22 weeks
|
To evaluate mean within-participant change in plasma progesterone and from the beginning and end of each Treatment Period, compared across treatment arms. This is measured in ng/mL |
22 weeks
|
|
Differences in measures of kidney function and proteinuria across each Treatment Period.
Časové okno: 22 weeks
|
To evaluate mean within-participant change in eGFR and UACR from the beginning and end of each Treatment Period, compared across treatment arms |
22 weeks
|
|
Differences in inflammation across each Treatment Period.
Časové okno: 22 weeks
|
To evaluate mean within- participant change in plasma NT-proBNP and hs-cTnT from the beginning and end of each Treatment Period, compared across treatment arms. |
22 weeks
|
|
Differences in plasma testosterone across each Treatment Period
Časové okno: 22 weeks
|
To evaluate mean within-participant change in plasma testosterone from the beginning and end of each Treatment Period, compared across treatment arms. This will be measured in ng/mL |
22 weeks
|
Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Differences in safety and tolerability between treatment groups (vica/empa; placebo/empa; and spiro/empa)
Časové okno: 22 weeks
|
To evaluate Incidence of TEAEs and SAEs |
22 weeks
|
|
Differences in safety and tolerability between vica/empa and placebo/empa across Treatment Period 1
Časové okno: 8 weeks
|
To evaluate change from baseline in clinical laboratory values (serum potassium) with the unit of measure mEq/L |
8 weeks
|
|
Differences in safety and tolerability between vica/empa and placebo/empa across Treatment Period 1.
Časové okno: 8 weeks
|
To evaluate change from baseline in clinical laboratory values (serum creatinine) measured in mg/dL |
8 weeks
|
|
Differences in safety and tolerability between vica/empa and placebo/empa across Treatment Period 1.
Časové okno: 8 weeks
|
To evaluate change from baseline in blood pressure measured in mm/Hg |
8 weeks
|
|
Differences in safety and tolerability between vica/empa and placebo/empa across Treatment Period 1.
Časové okno: 8 weeks
|
To evaluate change from baseline in heart rate measured in bpm units |
8 weeks
|
|
Differences in safety and tolerability between vica/empa and placebo/empa across Treatment Period 1.
Časové okno: 8 weeks
|
To evaluate change from baseline in QT (measured via 12-lead ECG) measured in milliseconds (ms) |
8 weeks
|
|
Differences in safety and tolerability between vica/empa and spiro/empa from the beginning of Treatment Period 1 until the end Treatment Period 2
Časové okno: 18 weeks
|
To evaluate change from beginning of Treatment Period 1 until the end of Treatment Period 2 in clinical laboratory values (serum creatinine) measured in mg/dL |
18 weeks
|
|
Differences in safety and tolerability between vica/empa and spiro/empa from the beginning of Treatment Period 1 until the end Treatment Period 2
Časové okno: 18 weeks
|
To evaluate change from beginning of Treatment Period 1 until the end of Treatment Period 2 in clinical laboratory values (serum potassium) measured in mEq/L |
18 weeks
|
|
Differences in safety and tolerability between vica/empa and spiro/empa from the beginning of Treatment Period 1 until the end Treatment Period 2
Časové okno: 18 weeks
|
To evaluate the change from the beginning of Treatment Period 1 until the end of Treatment Period 2 in blood pressure measured in mm/Hg |
18 weeks
|
|
Differences in safety and tolerability between vica/empa and spiro/empa from the beginning of Treatment Period 1 until the end Treatment Period 2
Časové okno: 18 weeks
|
To evaluate the change from beginning of Treatment Period 1 until the end of Treatment Period 2 in heart rate measured in bpm |
18 weeks
|
|
Differences in safety and tolerability between vica/empa and spiro/empa from the beginning of Treatment Period 1 until the end Treatment Period 2
Časové okno: 18 weeks
|
To evaluate the change from Treatment Period 1 until the end of Treatment Period 2 in QT measured on 12-lead ECG measured in milliseconds (ms) |
18 weeks
|
|
Difference in safety and tolerability between study arms across Treatment Period 3.
Časové okno: 4 weeks
|
To evaluate the difference in clinical laboratory values (serum creatinine) measured in md/dL between study arms across Treatment Period 3. |
4 weeks
|
|
Differences in Safety and Tolerability between study arms across Treatment Period 3.
Časové okno: 4 weeks
|
To evaluate the difference in clinical laboratory values (serum potassium) measured in mEq/L between study arms across Treatment Period 3. |
4 weeks
|
|
Difference in safety and tolerability between study arms across Treatment Period 3.
Časové okno: 4 weeks
|
To evaluate the difference in blood pressure measured in mmg/Hg between study arms across Treatment Period 3. |
4 weeks
|
|
Difference in safety and tolerability between study arms across Treatment Period 3.
Časové okno: 4 weeks
|
To evaluate the difference in heart rate measured in bpm between study arms across Treatment Period 3. |
4 weeks
|
|
Difference in safety and tolerability between study arms across Treatment Period 3.
Časové okno: 4 weeks
|
To evaluate the difference in QT by 12-lead ECG measured in milliseconds (ms) between study arms across Treatment Period 3. |
4 weeks
|
Spolupracovníci a vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: James L Januzzi, MD, Baim Institute for Clinical Research
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- BICR 2026-01
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .