Effect of Angiotensin Converting Enzyme and Sacubitril Valsartan in Patients After Bone Marrow Transplantation

Effect of Angiotensin Converting Enzyme and Sacubitril Valsartan in Left Atrial and Left Ventricular Performance, as Assessed With 3D Echocardiography, in Patients After Bone Marrow Transplantation.

The purpose of the present study is to investigate the effect of ACE inhibitors and the sacubitril-valsartan complex in bone marrow transplant patients by assessing cardiovascular and endothelial parameters in order to search for a potent protective role.

Study Overview

• Status: Unknown
• Conditions: Cardiotoxicity; Hematopoietic Stem Cell Transplantation
• Intervention / Treatment: Drug: ACE inhibitor, Sacubitril-Valsartan

Detailed Description

The purpose of the present study is to investigate the effect of ACE inhibitors and the sacubitril-valsartan complex in bone marrow transplant patients in preventing cardiotoxicity when administered immediately after transplantation.

The effect of medication will be studied in detail:

i) in global longitudinal strain of left ventricle (GLS), ii) in the volume change of the right and the left ventricle, through the cardiac cycle using 3D echocardiography, iii) in the Myocardial Work Index (MWI) of the left ventricle, with a strain -pressure curve study iv) in the 4D strain of the left atrium, v) in elastic properties of aorta (pulse wave velocity (PWV), central systolic pressure (CSBP-mmHg) and augmentation index (Aix%), vii) in permeability of glycocalyx and viii) in serum biomarker values, namely troponin I high sensitivity and atrial natriuretic peptide (NT-proBNP).

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Attiki
    • Athens, Attiki, Greece, 12462
      • Recruiting
      • "ATTIKON" University General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adolescents male and female
• that have just been treated with bone marrow transplantation due to haematological malignancies.

Exclusion Criteria:

• Coronary Artery Disease
• Permanent Atrial Fibrilation
• Signs of Left Ventricular Hypertrophy on electrocardiography or echocardiography
• Left ventricle Ejection Fraction<50% or segmental wall motion abnormalities of left ventricle
• More than moderate valvular disease
• Primary Myocardiopathy
• Blood Pressure<90 mmHg
• GFR<30 ml/min/1,73m2
• Unwilling to recruit
• Uncontrolled Arterial hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: ACE group; patients after bone marrow transplantation will be treated with ACE inhibitor	Drug: ACE inhibitor, Sacubitril-Valsartan; Search for Protective effect after chemotherapy and bone marrow transplantation; Other Names: Sacubitril-Valsartan
Other: Sacubitril Valsartan group; patients after bone marrow transplantation will be treated with sacubitril valsartan	Drug: ACE inhibitor, Sacubitril-Valsartan; Search for Protective effect after chemotherapy and bone marrow transplantation; Other Names: Sacubitril-Valsartan
Other: Control group; patients after bone marrow transplantation will be treated neither with ACE i nor with sacubitril valsartan	Drug: ACE inhibitor, Sacubitril-Valsartan; Search for Protective effect after chemotherapy and bone marrow transplantation; Other Names: Sacubitril-Valsartan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of treatment in Left Ventricular Function	Left Ventricular Function is assessed by calculating Ejection fraction by 3D echocardiography.	2 years
Effect of treatment in left ventricular function	Left Ventricular function is assessed by Global Longitudinal Strain by speckle tracking echocardiography	2 years
Effect of treatment in arterial stiffness	Arterial Stiffness is evaluated by Pulse Wave Velocity	2 years
Effect of treatment in glycocalyx thickness	Glycocalyx thickness is assessed by measuring perfused boundary region (PBR) of the sublingual arterial microvessels (range 5-25 µm	2 years

Collaborators and Investigators

• Sponsor: University of Athens
• Investigators: Principal Investigator: Ignatios Ikonomidis, Assoc. Prof, Athens University

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2019
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: September 14, 2019
• First Submitted That Met QC Criteria: September 16, 2019
• First Posted (Actual): September 17, 2019

Study Record Updates

• Last Update Posted (Actual): April 3, 2020
• Last Update Submitted That Met QC Criteria: April 1, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Cardio-oncology
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Wounds and Injuries; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Cardiotoxicity; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination; Angiotensin-Converting Enzyme Inhibitors
• Other Study ID Numbers: ACE_SAVA_3Decho_BMT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No