Currently recruiting trials investigating the role of nitrate and nitrite in Heart Failure

IdentifierTrial NameLead InvestigatorsDesignNo. of PatientsKey Inclusion CriteriaAgent and DoseDeliveryTreatment DurationPrimary/Powered OutcomesKey Additional Measures
NCT02713126Inorganic Nitrite to Amplify the Benefits and Tolerability of Exercise Training in Heart Failure with Preserved Ejection Fraction (HFpEF) (INABLE-Training)Barry Borlaug MDPhase II Randomized Double blind Placebo-controlled100HFpEF (LVEF >50%) NYHA II–IV, age >40 Enrolled in cardiac rehabilitation (exercise training)Sodium nitrite, 40 mg TDSOral Capsules12 wk• Peak VO2 on CPEX• Change in daily activity levels (accelerometer)
• Change in cardiac hemodynamics by Echo
• QoL assessment
ACTRN12615000906550Effects of Dietary Inorganic Nitrate Supplementation on Exercise Performance in Heart FailureProf. Jason D. AllenPhase I/II Randomized Placebo-controlled Crossover (minimum 2-wk washout)15 HFpEF +
15 HFrEF
HFpEF and HFrEF, age 18–85Sodium nitrate, ∼16 mmol ODBeetroot juice7 days• Peak VO2 on CPEX• Change in tissue oxygenation
• Time to exhaustion on CPEX• Plasma NOx levels
• Plasma nitrite levels• Change in mitochondrial function (muscle biopsy)
• Brachial artery flow-mediated dilatation
• Vascular stiffness (PWA and PWV)
• Hemodynamic parameters on Echo
NCT02918552Oral Nitrite for Older Heart Failure with Preserved Ejection Fraction (ONOH)Mark Gladwin MDPhase II Randomized Double blind Placebo-controlled16HFpEF (LVEF >40%), age >70Sodium nitrite, 20–40 mg TDSOral capsules8 wk active treatment• Peak VO2 on CPEX• Perceived fatiguability during exercise
• Change in daily activity levels (accelerometer)
• Measures of pulmonary hemodynamics (by right heart catheter)
• Skeletal muscle bioenergetics
• Plasma nitrate
NCT01682356Dietary Nitrates for Heart FailureLinda Peterson MD + Andrew Coggan MDPhase II Randomized Double blind Placebo-controlled Crossover (7-day washout)126HFrEF in transplant workup (NYHA III/IV) or pulmonary hypertension, age >18Dietary nitrate, 5 to 6 mmol ODBeetroot juice4 wk• Peak power with neuromuscular power test• Peak VO2 on CPEX
• Change in cardiac mass after LVAD• Pulmonary artery pressure by right heart catheter (if clinically indicated)
• Cardiac function by Echo or cardiac MRI (if clinically indicated)
• Submaximal exercise tolerance (6MWT)
NCT03511248Investigation of Dietary Nitrate Optimisation by Hyperuricaemia Stratification in Heart Failure (DiNOmo-HF)Dr. C.P. and A.A.Phase II Randomized Double blind Placebo-controlled92HFrEF (LVEF <40%) NYHA II/III, age >18 Elevated BNP/NT-proBNP
Stable medical therapy for 3 months
Dietary nitrate, 5 to 6 mmol ODBeetroot juice12 wk• Change in uric acid levels between strata (< and ≥ 9.8 mg/dl)• Sub-maximal exercise capacity (6MWT)
• LVEF• QoL questionnaire
• NOx levels• NT-proBNP and BNP
• Measures of oxidative stress
• Erythrocyte XOR activity
ACTRN12616000951459Feasibility and Effects of Inorganic Nitrate in Acute Decompensated Heart Failure (FINO-ADHF)Prof. Christopher NeilPhase I/II Randomized Double blind Placebo-controlled40Acute decompensated HF, age >18Sodium nitrate, 8.4 mmol over four 12-h intervalsBeetroot juice + capsules48 h• Plasma NOx levels• Vascular stiffness (PWA and PWV)
• A change in vasorelaxation as assessed by systemic vascular resistance index• Change in renal function by cystatin C levels
• Change in oxygenation using pulse oximetry
• Dyspnea relief
• Cardiac troponin T
• Change in natriuresis measured by urinary sodium
• Changes in cardiac function by Echo
NCT02797184Inorganic Nitrate and Exercise Performance in Heart Failure (iNIX-HF): Dose ResponseLinda Peterson MD + Andrew Coggan MDPhase II
Double blind Dose crossover (7-day washout)
25HFrEF (LVEF <45%) NYHA II–IV, age 18–74 Stable medical therapy for 30 daysPotassium nitrate, 10 and 20 mmol onceOral capsules7 days between acute dosing• Peak VO2 on CPEX (acute: 2.5 h postdose)• Peak muscle power (quadriceps)
• Plasma NOx levels
• Breath NO level
ACTRN12613000689774 (withdrawn)Randomized double blind controlled pilot trial investigating the effect dietary nitrate in the treatment of acute decompensated heart failureProf. David KayePhase II Randomized Double blind Placebo-controlled20Acute decompensated HF (LVEF <40%) NYHA III/IV, age 18–75Dietary nitrate, 5 to 6 mmolBeetroot juice5 days• Change in endothelial function by EndoPAT
• QoL questionnaire
• Treatment success: a composite of patient-reported improvement in dyspnea with no criteria for failure
NCT03658174Upregulating the Nitric Oxide Pathway to Restore Autonomic Phenotype (UNTRAP)Dr. Zakiryya Vali and Dr. Andre NgDouble blind Placebo-controlled Crossover (unspecified washout)20HFrEF (LVEF <40%) NYHA II/III, age >18 Sinus rhythm with ICD in situDietary nitrate, 5 to 6 mmolBeetroot juice4 wk with each intervention (unspecified washout)Change in:• Systolic and diastolic function by Echo
• heart rate variability• Peak VO2 on CPEX
• QT variability index• QoL questionnaire
• Regional Restitution Instability Index (marker of ventricular arrhythmia and SCD)
• Peak ECG Restitution Slope (marker of ventricular arrhythmia and SCD)
  • CPEX, cardiopulmonary exercise test; Echo, echocardiography; ICD, implantable cardioverter-defibrillator; LVAD, left ventricular assist device; 6MWT, 6-minute walk test; OD, once daily; PWA, pulse wave analysis; QoL, quality of life; SCD, sudden cardiac death; TDS, three times daily; VO2, maximal oxygen consumption.