Table 1.
Current Landscape of Multi-Center Randomized Controlled Trials in Heart Failure with Preserved Ejection Fraction
| Trial name | Sponsor | Treatment | Study design | Targeted approach |
|---|---|---|---|---|
| ATTR-ACT | Pfizer | Tafamadis (TTR stabilizer) | Phase 3 RCT + extension study | TTR cardiac amyloidosis |
| BeAT-HF | CVRx | Barostim Neo (carotid baroreceptor stimulator) | Phase 3 RCT | None |
| D-HART2 | NIH | Anakinra (IL-1 blocker) | Phase 2 RCT | High-sensitivity CRP > 2.0 mg/dl |
| EMPEROR-Preserved | Boehringer-Ingelheim | Empaglaflozin (SGLT-2 inhibitor) | Phase 3 RCT | None |
| ENDEAVOUR | Alnylam | Resuviran (TTR RNAi) | Phase 2 RCT | TTR cardiac amyloidosis |
| FAIR-HFpEF | Investigator-initiated | Intravenous iron (ferric carboxymaltose) | Phase 2 RCT | Iron deficiency (ferritin <100 ng/mL or ferritin 100–299 ng/mL plus transferrin saturation <20%) |
| INDIE-HFpEF | NIH, Aries | Inhaled nitrite | Phase 2 RCT, cross-over | None |
| KNO3CK-OUT | NIH | Potassium nitrate (inorganic nitrate) | Phase 2 RCT, cross-over | None |
| LIBERTY | Gilead | Eleclazine (late INa+ inhibitor) | Phase 2 RCT | Hypertrophic cardiomyopathy |
| PANACHE | Bayer | Neladenoson bialanate (adenosine partial A1 receptor agonist) | Phase 2 RCT | None |
| PARAGON | Novartis | Sacubitril/valsartan (angiotensin receptor-neprilysin inhibitor) | Phase 3 RCT | None |
| PARALLAX | Novartis | Sacubitril/valsartan (angiotensin receptor-neprilysin inhibitor) | Phase 3 RCT | None |
| PRESERVED-HF | AstraZeneca* | Dapaglaflozin (SGLT-2 inhibitor) | Phase 3 RCT | Diabetic/pre-diabetic HFpEF |
| REDUCE LAP-HF I | Corvia | Interatrial shunt device | Phase 2 RCT, cross-over | Left heart failure-predominant HFpEF (PCWP≫RAP) |
| REDUCE LAP-HF II | Corvia | Interatrial shunt device | Phase 3 RCT, cross-over | Left heart failure-predominant HFpEF (PCWP≫RAP) |
| SERENADE | Actelion | Macitentan (endothelin receptor antagonist) | Phase 2 RCT | CpcPH-HFpEF |
| SOUTHPAW | United Therapeutics | Oral treprostinil (prostacyclin analogue) | Phase 2 RCT | CpcPH-HFpEF |
Investigator-initiated trial via Mid-America Heart Institute, Kansas City, Missouri, USA
Note: the trials listed above are not meant to be a comprehensive list; rather they represent the majority of the major randomized, multi-center HFpEF clinical trials that were ongoing at the time of publication of the manuscript.
TTR = transthyrtein; IL-1 = interleukin-1; SGLT-2 = sodium-glucose transporter-2; RNAi = RNA interference; INa+ = inward sodium current; RCT = randomized controlled trial; CRP = C-reactive protein; HFpEF = heart failure with preserved ejection fraction; PCWP≫RAP = pulmonary capillary wedge pressure greater than right atrial pressure; CpcPH= combined post- and pre-capillary pulmonary hypertension.