NCT02742129

Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 105 (actual)
• Sponsor: Adrian Hernandez · Academic / Other
• Sex: All
• Age: 40 Years
• Healthy volunteers: Not accepted

Summary

A randomized, double-blind, placebo-controlled crossover study to assess the effect of inorganic nitrite (NO2) on aerobic capacity (peak VO2) after four weeks of dosing. Approximately 100 participants will be enrolled in this 2\*2 crossover study.

Detailed description

Screen potential HFpEF patients for eligibility criteria and interest Study Visit 1 • Initiate consent process and obtain written informed consent. * Confirm with the participant that HF symptoms are the primary limitation to activity. If so, they proceed to CPET screening. If not, they are considered a screen fail. * Obtain baseline bloods \*- CBC, complete chemistry panel, biomarkers, biorepository and genetics (if agreed to participate) . * Obtain CPET to verify patient eligibility peak VO2 ≤ 75% predicted and RER ≥ 1.0 (within 3 days prior to randomization) and establish baseline value. * Qualifying patients perform additional baseline studies: history, assess NYHA class, physical exam, ECG, and KCCQ. * Open label, single-dose run-in where patient receives maximal dose (80 mg) inhaled inorganic nitrite. Patients who do not tolerate the run-in are considered screen failures. * Randomize qualifying patients. * Dispense phase-1 study drug, nebulizers and accelerometers * Participants take no study drug for two weeks (baseline). * Participants take 46 mg study drug at a minimum of 4 hours apart, 3 times a day, during active part of the day for 7 days. * Participants take 80 mg study drug at a minimum of 4 hours apart, 3 times a day, during active part of the day until returning for study visit 2 (at least 42 days but up to 49 days post-baseline visit). * If side effects develop, participants can down-titrate to the previous dose. * Participants are called frequently to reinforce study procedures and assess compliance. Study Visit 2 (42-49 Days Post Study Visit 1) • Participant holds study drug on day of visit. * Review history, assess NYHA class, perform physical exam and KCCQ. * Obtain blood draws \*\* - CBC, complete chemistry panel, biomarkers, biorepository (if agreed to participate). * Obtain limited echocardiogram \*\*. * Perform CPET with Study Drug administered immediately before starting the CPET (primary endpoint). * Change out accelerometer and dispense phase-2 study drug. * Participants take no study drug for two weeks (washout). * Participants take 46 mg study drug at a minimum of 4 hours apart, 3 times a day, during active part of the day for 7 days. * Participants take 80 mg study drug at a minimum of 4 hours apart, 3 times a day, during active part of the day until returning for study visit 3 (at least 42 but up to 49 days after study visit 2). * If side effects develop Participants can down-titrate to the previously tolerated dose. * Participants are called frequently to reinforce study procedures and assess compliance. Study Visit 3 (42-49 Days Post Study Visit 2) • Participant holds study drug on day of visit. • Review history, assess NYHA class, perform physical exam and KCCQ * Obtain blood draws\*\* - CBC, complete chemistry panel, biomarkers, biorepository (if agreed to participate). * Obtain limited echocardiogram\*\*. * Perform CPET with Study Drug administered immediately before starting the CPET (primary endpoint). * Return accelerometer and phase-2 study drug. * End of study drug (phase out). Phone Visit and End of Study (14 Days Post Study Visit 3) • A final phone visit is conducted to assess for adverse events. \*Visit 1: baseline blood draw needs to be completed prior to the CPET (if this is not feasible, then they cannot be obtained for at least 3 hours post the CPET and prior to the run-in test dose). \*\*Visit 2 and Visit 3: blood draws and limited echo need to be obtained prior to study drug administration (if this is not feasible, then it cannot be obtained for at least 3 hours post study drug administration)

Conditions

• Heart Failure

Interventions

Type	Name	Description
DRUG	Nebulized Sodium Nitrite	Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day.
DRUG	Placebo	Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day.

Timeline

• Start date: 2016-08-10
• Primary completion: 2017-12-13
• Completion: 2017-12-27
• First posted: 2016-04-18
• Last updated: 2019-03-13
• Results posted: 2019-03-13

Locations

20 sites across 1 country: United States