Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF — INDIE-HFpEF  

Heart Failure Clinical Trial

Official title: Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF

Status Completed

Clinical Trial 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.

Clinical Trial 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) ;

Related Conditions & MeSH terms

• Heart Failure

• NCT number: NCT02742129
• Study type: Interventional
• Source: Duke University
• Status: Completed
• Phase: Phase 2
• Start date: August 10, 2016
• Completion date: December 27, 2017