Table 3. Ongoing clinical trials.
| NCT number | Trial title | Drugs | Mechanism of action | Trial disease state | Main prim. endpoint | Number participants | Study type | Trial phase | Trial status | Main RV function-specific endpoints |
|---|---|---|---|---|---|---|---|---|---|---|
| Targeting PA vasoconstriction | ||||||||||
| NCT03217331 | CRD-102 for Right Heart Failure in Patients with Left Ventricular Assist Devices | CRD-102 (oral milrinone) | PDE3 inhibitor | RHF after assist device implant | Number of adverse events | 6 | N/A | 1 + 2 | Completed | – |
| NCT02554903 | A Prospective, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of Macitentan in Patients with Pulmonary Hypertension After Left Ventricular Assist Device Implantation | Macitentan | ETA | PH | PVR | 57 | Randomized | 2 | Completed | – |
| NCT03356353 | Sildenafil for the Prevention of Right Heart Failure Following Continuous-Flow Left Ventricular Assist Device Implantation (The REVAD Study) | Sildenafil | PDE5 inhibitor | End stage heart failure | PVR | 24 | N/A | 3 | Recruiting | RHF |
| NCT03624010 | Open-Label Rollover Study of Levosimendan in Patients with Pulmonary Hypertension with Heart Failure and Preserved Left Ventricular Ejection Fraction (PH-HFpEF) | Levosimendan | Calcium sensitizer | HFpEF, PH, RHF | Number of adverse events | 36 | N/A | 2 | Active, not recruiting | – |
| NCT03659851 | Pretreatment with Levosimendan In Patients Undergoing Left Ventricular Assist Device Implantation | Levosimendan | Calcium sensitizer | RHF, Left Heart Failure | Laboratory parameters | 50 | Case-Crossover | – | Recruiting | – |
| NCT03541603 | A Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Pulmonary Hypertension Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction (PH-HFpEF) | Levosimendan | Calcium sensitizer | Secondary PH (HFpEF), RHF | PCWP | 36 | Randomized | 2 | Completed | – |
| Targeting adrenoceptors | ||||||||||
| NCT00240656 | Spironolactone Combined with Captopril and Carvedilol for the Treatment of Patients with Pulmonary Arterial Hypertension Associated with Congenital Heart Disease—Focus on Pulmonary Artery Remodeling | Spironolactone, captopril, carvedilol | Aldosterone antagonist, ACE antagonist, β-blocker | PH (congenital heart disease) | Dyspnoea score, Exercise capacity, PAP | – | Non-randomized | 1 | Completed | RVAT, RVET, RVET/RVAT |
| Targeting the renin-angiotensin-aldosterone system | ||||||||||
| NCT01712620 | A Pilot Study of the Effect of Spironolactone Therapy on Exercise Capacity and Endothelial Dysfunction in Pulmonary Arterial Hypertension | Spironolactone | Aldosterone antagonist | PAH | Walk distance | 70 | Randomized | 2 | Recruiting | RV function |
| NCT03344159 | Spironolactone Therapy in Chronic Stable Right HF Trial (STAR-HF) | Spironolactone | Aldosterone antagonist | PAH, PH, RV cardiomyopathy | NT-proBNP | 40 | Randomized | 4 | Suspended (COVID-19) | RV EF |
| NCT03177603 | An Open-label, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of GSK2586881 in Participants with Pulmonary Arterial Hypertension | GSK2586881 (rhACE2) | rhACE2 | PH | PVR, CO, mPAP | 23 | Non-randomized | 2 | Completed | – |
| NCT03177603 | A Dose-escalation Study in Subjects with Pulmonary Arterial Hypertension (PAH) | GSK2586881 (rhACE2) | rhACE2 | PAH | PVR, CO, mPAP | 23 | Open label | 2 | Completed | – |
| Targeting energy metabolism | ||||||||||
| NCT03629340 | Phase II Trial of Metformin for Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction | Metformin | Metabolic modulator | PH (HFpEF) | mPAP | 32 | Randomized | 2 | Active, not recruiting | – |
| NCT03617458 | Interventions Against Insulin Resistance in Pulmonary Arterial Hypertension | Metformin | Metabolic modulator | PAH | Walk distance, change in WHO functional class | 39 | Randomized | 2 | Recruiting | TAPSE, RVEF, RVFA, RV longitudinal strain |
| NCT01083524 | A Phase I, Open-Label, Two Centre Study to Evaluate Dichloroacetate (DCA) in Advanced Pulmonary Arterial Hypertension. | DCA | Metabolic modulator + PDK inhibitor | PAH | Safety and tolerability of DCA | 30 | Non-randomized | 1 | Completed | RV size/function |
| Targeting inflammation and oxidative stress | ||||||||||
| NCT02036970 | A Dose-Ranging Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Pulmonary Hypertension | Bardoxolone methyl | Nrf2 inducer + NF-κB inhibitor | PAH, PH | Walk distance | 166 | Randomized | 2 | Completed | – |
| NCT02657356 | A Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Connective Tissue Disease-associated Pulmonary Arterial Hypertension | Bardoxolone methyl | Nrf2 inducer + NF-κB inhibitor | Connective tissue disease-associated PAH | Walk distance | 202 | Randomized | 3 | Terminated (COVID-19) | – |
| NCT03068130 | An Extended Access Program to Assess Long-term Safety of Bardoxolone Methyl in Patients with Pulmonary Hypertension | Bardoxolone methyl | Nrf2 inducer + NF-κB inhibitor | PH | Long-term safety | 414 | N/A | 3 | Recruiting | – |
| NCT03449524 | Phase 2 Multicenter, Double-Blind, Placebo Controlled, Efficacy, Safety, and Pharmacokinetic Study of 2 Doses of CXA-10 on Stable Background Therapy in Subjects with Pulmonary Arterial Hypertension | CXA-10 | Nitrated fatty acid compound | PAH | RVEF, PVR | 96 | Randomized | 2 | Recruiting | – |
| NCT03738150 | A Phase 2a Single-Arm, Open-Label, Multicenter Exploratory Study to Assess the Effects of Sotatercept (ACE-011) for the Treatment of Pulmonary Arterial Hypertension | Sotatercept | TGF-β ligand trap (soluble activin receptor type 2A IgG-Fc fusion protein) | PAH | Peak oxygen uptake | 25 | N/A | 2 | Recruiting | – |
| Targeting miRNA | ||||||||||
| NCT04045405 | Phase I, Randomized, Double-blind, Placebo-controlled Study to Assess Safety, PK and PD Parameters of CDR132L in Patients with Stable Heart Failure of Ischemic Origin (NYHA 1-3) | CDR132L | miRNA-132 inhibitor | Heart failure | Incidence and severity of adverse events | 28 | Randomized | 1 | Completed | – |
| NCT03603431 | A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose-escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Activity of MRG-110 Following Local Intradermal Injection After Skin Excisional Wound Creation in Normal Healthy Volunteers | MRG-110 | miRNA-92a inhibitor | Healthy volunteer | Number of adverse events | 42 | Randomized | 1 | Completed | – |
ACE, angiotensin converting enzyme; ASK1, apoptosis signal-regulating kinase 1; DCA, dichloroacetate; ETA, endothelin receptor antagonist; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; mPAP, mean pulmonary arterial pressure; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B-cells; Nrf2, nuclear factor erythroid 2-related factor 2; PAH, pulmonary arterial hypertension; PCWP, pulmonary capillary wedge pressure; PDK, pyruvate dehydrogenase kinase; PAH, pulmonary arterial hypertension; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; RHF, right heart failure; RV, right ventricle; RVEF, right ventricular ejection fraction; RVAT, right ventricular acceleration time, RVET, right ventricular ejection time.