Targeting Pulsatile Load to Increase Exercise Capacity and Quality of Life After Aortic Valve Replacement for Severe Aortic Stenosis (PULSE AS)

NCT03483051 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 828994
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The current trial is designed to assess the safety and efficacy of sustained oral administration of inorganic nitrate in patients with severe aortic stenosis and to assess the mechanisms by which inorganic nitrate enhances oxygen uptake and exercise capacity in this population.

Conditions

Aortic Valve Stenosis

Keywords

aortic stenosis, aortic valve replacement

Outcome Measures

Primary Outcomes (3)

• Total Work Performed During a Maximal-effort Exercise Test

  The effect of KNO3 on exercise capacity, quantified as Total work performed during a maximal-effort exercise test;

  9 weeks

• Peak Oxygen Uptake (VO2) During a Maximal Effort Exercise Test

  The effect of KNO3 on exercise capacity, quantified as: Peak oxygen consumption (VO2) during a symptom-limited maximal effort exercise test.

  9 weeks

• Quality of Life Score

  The effect of KNO3 on quality of life, assessed using the Kansas City Cardiomyopathy Questionnaire.

  9 weeks

Secondary Outcomes (4)

• Systemic Vasodilator Response to Exercise

  9 weeks

• Left Ventricle Diastolic Function

  9 weeks

• Myocardial Systolic Strain

  9 weeks

• Late Systolic Left Ventricle Load

  9 weeks

Study Arms (2)

Potassium Nitrate (KNO3)

EXPERIMENTAL

Capsules containing 18 mmoles of KNO3 per day, given as one capsule (6 mmoles) three times a day for 4 weeks.

Drug: Potassium Nitrate

Potassium Chloride

SHAM COMPARATOR

Capsules containing 18 mmoles of KCl per day, given as one capsule (6 mmoles) three times a day for 4 weeks.

Drug: Potassium Chloride

Interventions

Potassium Nitrate DRUG

Potassium nitrate capsules will consist of potassium nitrate (KNO3-) crystals \[610 mg, corresponding to 6.03 mmoles of NO3-\] with 190mg of lactose monohydrate, spray dried, NF. The dose for this trial will be 18 mmoles of NO3-per day, given as one capsule (6 mmoles) three times a day.

Potassium Nitrate (KNO3)

Potassium Chloride DRUG

Potassium chloride capsules will consist of potassium chloride (KCl), granular, USP (450mg) plus lactose monohydrate, spray dried, NF (300mg). The dose for this trial will be 18 mmoles of KCl per day, given as one capsule (6 mmoles) three times a day.

Potassium Chloride

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 50-90 years of age
• Diagnosis of severe aortic stenosis prior to aortic valve repair
• Successful trancatheter aortic valve repair via transfemoral procedural approach or successful surgical aortic valve repair at least three months prior to enrollment
• Stable medical therapy: no addition/removal/changes in anti-hypertensive medications, or beta-blockers in the preceding 30 days.

You may not qualify if:

• Supine systolic blood pressure (SBP) \< 100 mmHg OR supine diastolic blood pressure (DBP) \<60 mmHg
• Poorly controlled hypertension, as defined as SBP \> 160 mmHg OR DBP \> 100 mmHg
• Pregnancy. Women of childbearing potential will undergo a pregnancy test during the screening visit
• Atrial fibrillation within the prior 8 weeks before enrollment
• Inability/unwillingness to exercise
• Moderate or greater mitral regurgitation or aortic/peri-valvular regurgitation, any degree of mitral stenosis, severe right-sided valvular disease, or presence of a mitral prosthetic valve.
• Moderate or severe patient prosthesis mismatch, as defined by Effective Orifice Area Index \< 0.85 cm2/m2
• Hypertrophic, infiltrative, or inflammatory cardiomyopathy
• Pericardial disease
• Current angina
• Acute coronary syndrome or coronary intervention within the past 2 months
• Primary pulmonary arteriopathy
• Clinically significant lung disease as defined by: Chronic Obstructive pulmonary disease meeting Stage III or greater GOLD criteria, treatment with oral steroids within the past 6 months for an exacerbation of obstructive lung disease, or the use of daytime supplemental oxygen
• Ischemia on stress testing without subsequent revascularization (during the screening visit)
• Treatment with phosphodiesterase inhibitors that cannot be withheld

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Aortic Valve Stenosis

Interventions

potassium nitrate; Potassium Chloride

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Potassium Compounds

Limitations and Caveats

Efficacy data analyses will not be performed as they are not meaningful due to enrollment of only three (3) subjects.

Results Point of Contact

• Title: Dr. Julio Chirinos
• Organization: University of Pennsylvania

juliochi@pennmedicine.upenn.edu

215-200-7779

Study Officials

• Julio Chirinos, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In this phase IIb, double-blind, cross-over trial, we will assign 22 subjects who are post-TAVR for severe AS to: (A) Potassium nitrate administered by mouth at a dose of 6 mEq three times daily for 4 weeks, or (B) Potassium chloride (KCl) at identical doses. The order of the interventions (AB-BA design) will be randomized, with a 1-week washout period separating each intervention. A crossover design will enable each subject to receive both treatments.

Study Record Dates

• First Submitted: February 15, 2018
• First Posted: March 29, 2018
• Study Start: May 1, 2018
• Primary Completion: March 13, 2019
• Study Completion: May 23, 2019
• Last Updated: June 17, 2020
• Results First Posted: March 11, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)