Haemodynamic Effects of Dobutamine in Patients With Wild-type Transthyretin Amyloid Cardiomyopathy (ATTRwt)

NCT06318260 | Recruiting Phase 1

• 1 other identifier: 2023-508298-10-00
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test the effects of the inotropic drug named dobutamine, in patients with wild-type Transthyretin Amyoid Cardiomyopathy (ATTRwt). The main questions it aims to answer are:

• What are the effects of increasing dosages of dobutamine infusion on cardiac output and filling pressures in patients with symptomatic ATTRwt.
• Safety of dobutamine infusion in this patient population. Participants will be given increasing dosages of dobutamine infusion, and its effect on cardiac output and filling pressures will be assessed non-invasively by echocardiography, and invasively by right heart catheterization, simultaneously.

Conditions

ATTR Amyloidosis Wild Type

Keywords

Cardiac amyloidosis; Inotropic; ATTR-CM; Transthyretin amyloid cardiomyopathy; Dobutamine; wild type ATTR

Outcome Measures

Primary Outcomes (1)

• Cardiac output

  Mean cardiac output increase by 10%, evaluated by the thermodynamic invasive methods.

  Evaluated at every dobutamine dose-level, and at the end of infusion.

Secondary Outcomes (5)

• Increase in invasively measured SVI by ≥ 20%.

  Evaluated at every dobutamine dose-level, and at the end of infusion.

• Reduction in mean PAWP and/or mPAP by 10 %.

  Evaluated at every dobutamine dose-level, and at the end of infusion.

• Increase in LVEF and LV-global longitudinal strain (LV-GLS) of absolute 10 %.

  Evaluated at every dobutamine dose-level, and at the end of infusion.

• Correlation between echo- and invasive measured SVI, and CO.

  Evaluated at every dobutamine dose-level, and at the end of infusion.

• Rate of complications (i.e. Systolic blood pressure drop < 90 mmHg, arrhythmias)/symptomatic side effects.

  Evaluated at every dobutamine dose-level, at the end of infusion, and during the 2 hours recovery period.

Study Arms (1)

ATTRwt

EXPERIMENTAL

Dobutamine (Dobutrex®) infusion.

Drug: Dobutrex

Interventions

Dobutrex DRUG

Dobutamine (Dobutrex®) infusion. will be performed with a stepwise dobutamine dosage increase every 5 minutes (2,3,5,10,20 ug/kg/min). Dobutamine dosage will only be increased to 40 ug/kg/min in participants with ongoing beta-blocker treatment to ensure an appropriate dobutamine response. As dobutamine and its metabolites are excreted renally, the dose will be reduced to max 10 ug/kg/min in participants with eGFR below 30 mL/min/1,73 m2. Echocardiography, blood pressure, heart rate, and invasive pressure and flow measurements will be obtained before the infusion starts, at each infusion stage, and during the recovery period after the infusion is stopped.

Also known as: Dobutamine

ATTRwt

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• ATTRwt, diagnosis confirmed by genetic testing, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy and/or endomyocardial biopsy.
• Treated with loop diuretics.
• New York Heart Association class II-IV.
• Age ≥ 65 years.
• Left ventricular ejection fraction (LVEF) \< 50 % and/or SVI assessed by echocardiography \< 35 ml/m2.
• Thorough oral and written informed consent to participate in the study.

You may not qualify if:

• Moderate to severe aortic stenosis (participants with aortic sclerosis will not be excluded).
• Other significant valvular diseases.
• Known severe coronary artery diseases: left main stem stenosis or 3-vessel disease, or recent acute myocardial infarction (\< 4 weeks).
• Contraindications to the use of dobutamine: Known allergy to dobutamine or sulfite, phaeochromocytoma or ventricular tachycardia (VT).
• End stage renal disease (eGFR of less than 15 mL/min/1,73 m2).

Sponsors & Collaborators

• Steen Hvitfeldt Poulsen: lead

Study Sites (1)

Department of Cardiology, Aarhus University Hospital

Aarhus, 8200, Denmark

RECRUITING

MeSH Terms

Conditions

Amyloid Neuropathies, Familial

Interventions

Dobutamine

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies

Intervention Hierarchy (Ancestors)

Catecholamines; Amines; Organic Chemicals; Phenethylamines; Ethylamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Central Study Contacts

Ali Hussein Jaber Mejren, MD

CONTACT

0045 91 65 18 48; alimej@clin.au.dk

Steen Hvitfeldt Poulsen, MD,PhD,DMSci

CONTACT

steepoul@rm.dk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, DMSc.

Model Details: Prospective, single-centre, one arm clinical explorative study, with consecutive enrolment.

Study Record Dates

• First Submitted: March 12, 2024
• First Posted: March 19, 2024
• Study Start: April 8, 2024
• Primary Completion: September 1, 2025
• Study Completion: March 1, 2026
• Last Updated: April 17, 2024

Record last verified: 2024-04

Locations

DK (1)