Inhaled Iloprost and Exercise Hemodynamics and Ventricular Performance in Heart Failure With Preserved Ejection Fraction

NCT03620526 | Unknown Phase 4 DMC

• 1 other identifier: 201704075MIND
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

BACKGROUND There is no effective medical treatment for heart failure with preserved ejection fraction (HFpEF). Increases in pulmonary capillary wedge pressure (PCWP) develop in patients with HFpEF. Prostacyclin analogo can possible reduced PA pressure along with PWCP pressure, as with exercise. OBJECTIVES This study try to determine whether inhlalation of iloprost improves exercise hemodynamics and cardiac reserve in HFpEF. METHODS In a double-blind, randomized, placebo-controlled, parallel-group trial, subjects with HFpEF underwent invasive cardiac catheterization with simultaneous expired gas analysis at rest and during exercise, before and 15 min after treatment with either inhaled iloprost or matching placebo.

Conditions

Heart Failure With Normal Ejection Fraction

Keywords

Iloprost; Heart failure with preserved ejection fraction; hemodynamic; Pulmonary wedge pressure

Outcome Measures

Primary Outcomes (1)

• Pulmonary wedge pressure changes after exercise measured by swan-ganz catheter (effect of inhalation of drug[efficacy])

  Exercise pulmonary wedge pressure changes measured by swan-ganz catheter

  15 minutes after inhalation of drugs

Secondary Outcomes (3)

• Resing pulmonary wedge pressure measured by swan-ganz catheter (effect of inhalation of drug[efficacy])

  15 minutes after inhalation of drugs

• Resting cardiac output as assessed by direct Fick method and heart rate (effect of inhalation of drug[efficacy])

  15 minutes after inhalation of drugs

• Resting pulmonary vascular resistance as assessed by direct Fick method and heart rate (effect of inhalation of drug[efficacy])

  15 minutes after inhalation of drugs

Study Arms (2)

Iloprost

EXPERIMENTAL

patients received inhaled iloprost 10 mcg/mL x 1 dose after baseline and exercise test and then received measurements for hemodynamic data again for both baseline and after exercise test.

Drug: Iloprost

Placebo

PLACEBO COMPARATOR

patients received inhaled normal saline with the same amount x 1 dose after baseline and exercise test and then received measurements for hemodynamic data again for both baseline and after exercise test.

Drug: Placebo

Interventions

Iloprost DRUG

Investigators performed cardiac catheterization as previously described. Hemodynamic values were recorded for the first exercise phase (before any drug administration) and after return to steady state baseline hemodynamic values, and the second exercise phase (after drug administration). Subjects were randomized 1:1 to inhalation of placebo (normal saline solution) or iloprost (50 mg/kg/min) (Bayer Pharmaceuticals, Scottsdale, Ari-zona) for 5 min. The iloprost/placebo inhalation were identical in appearance and prepared by the research pharmacy, ensuring double-blinding of inhalation content. After finishing inhalation process for 10 min, hemodynamic measurements were repeated at rest, followed by repeat supine exercise at a 20-W workload for 6 min, identical to the study's first phase.

Iloprost

Placebo DRUG

Investigators performed cardiac catheterization as previously described. Hemodynamic values were recorded for the first exercise phase (before any drug administration) and after return to steady state baseline hemodynamic values, and the second exercise phase (after drug administration). Subjects were randomized 1:1 to inhalation of placebo (normal saline solution) or iloprost (50 mg/kg/min) (Bayer Pharmaceuticals, Scottsdale, Ari-zona) for 5 min. The iloprost/placebo inhalation were identical in appearance and prepared by the research pharmacy, ensuring double-blinding of inhalation content. After finishing inhalation process for 10 min, hemodynamic measurements were repeated at rest, followed by repeat supine exercise at a 20-W workload for 6 min, identical to the study's first phase.

Placebo

Eligibility Criteria

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

You may qualify if:

• presence of typical HF symptoms and signs
• LV ejection fraction ≥ 50
• elevated levels of NT-proBNP (at least \>125 pg/ml)
• echocardiographic structural (a left atrial volume index \> 34 mL/m2 or a left ventricular mass index ≥115 g/m2 for males and ≥95 g/m2 for females) or functional alterations (E/e'≥13 and a mean e' septal and lateral wall \< 9 cm/s).

You may not qualify if:

• chronic renal failure (creatinine \> 250 μmol/L)
• significant hepatic disease, significant coronary artery disease (CAD) (coronary artery stenosis \>70% without intervention or positive stress test),
• secondary hypertension,
• pericardial disease
• significant valvular heart disease (\>mild stenosis, \>moderate regurgitation),
• active cancer,
• cor pulmonale
• congenital heart disease
• high-output heart failure
• subjects receiving long-term treatment with phosphodiesterase 5 in-hibitors
• chronic atrial fibrillation.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

RECRUITING

Related Publications (3)

• Borlaug BA, Koepp KE, Melenovsky V. Sodium Nitrite Improves Exercise Hemodynamics and Ventricular Performance in Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol. 2015 Oct 13;66(15):1672-82. doi: 10.1016/j.jacc.2015.07.067.

  PMID: 26449137 RESULT

• Chen ZW, Huang CY, Cheng JF, Chen SY, Lin LY, Wu CK. Stress Echocardiography-Derived E/e' Predicts Abnormal Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction. Front Physiol. 2019 Dec 3;10:1470. doi: 10.3389/fphys.2019.01470. eCollection 2019.

  PMID: 31849715 DERIVED

• Huang CY, Lee JK, Chen ZW, Cheng JF, Chen SY, Lin LY, Wu CK. Inhaled Prostacyclin on Exercise Echocardiographic Cardiac Function in Preserved Ejection Fraction Heart Failure. Med Sci Sports Exerc. 2020 Feb;52(2):269-277. doi: 10.1249/MSS.0000000000002145.

  PMID: 31479003 DERIVED

MeSH Terms

Interventions

Iloprost

Intervention Hierarchy (Ancestors)

Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• CHO-KAI WU, MD, PhD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

CHO-KAI WU, MD, PhD

CONTACT

886-23123456; chokaiwu@yahoo.com.tw

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2018
• First Posted: August 8, 2018
• Study Start: November 29, 2017
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2020
• Last Updated: August 14, 2019

Record last verified: 2019-08

Locations

TW (1)