Clinical trial NCT06406517: Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
Official title: Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Congenital Heart Disease
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Bracco Imaging S.p.A.
First posted: 2024-05-09
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This will be a prospective, single center, parallel group, double-blinded, randomized clinical trial. The study will be conducted at UC San Diego MRI suites. Study participants will be randomized into one of four study arms prior to their MRI: Gadopiclenol 0.075 mmol/kg, gadopiclenol 0.10 mmol/kg, gadopiclenol 0.15 mmol/kg, gadobenate dimeglumine 0.15 mmol/kg (standard of care).
Primary purpose: OTHER

Brief summary: The goal of this clinical trial is to learn how well and at what doses gadopiclenol, a new intravenous (IV) contrast agent used for MRI, works to produce high-quality MRI images of the heart, in patients with a history of congenital heart disease, when compared to gadobenate dimeglumine, the IV contrast agent that is normally used at our institution for heart (cardiac) MRI. The main questions it aims to answer are:

* Does using gadopiclenol result in similar or superior image quality, similar signal-to-noise ratio (SNR), and similar flow measurements with 4-dimensional (4D) flow cardiac MRI when compared to gadobenate dimeglumine?
* At what dose(s) does gadopiclenol result in similar image quality (using the above metrics) for cardiac MRI when compared to gadobenate dimeglumine?

Researchers will compare cardiac MRI images obtained after administration of gadopiclenol to cardiac MRI images obtained after administration of gadobenate dimeglumine (called the standard of care treatment) to see if the images are of similar or superior quality.

Participants will:

* Be randomized to receive either gadopiclenol at one of three different doses or gadobenate dimeglumine before their congenital heart cardiac MRI
* Undergo their congenital heart cardiac MRI as they would during the course of normal clinical care.

Detailed description: At the University of California San Diego (UCSD), we have developed a premier advanced clinical cardiovascular imaging program, which is a critical component of our Adult Congenital Heart Association (ACHA)-accredited adult congenital heart program. Central to these programs is 4D Flow MRI, which enables hemodynamic assessment of patients with repaired and unrepaired congenital heart disease. Adults with congenital heart disease require routine MRI for surveillance and management of complications of disease and repairs, and 4D Flow allows us to reliably perform these exams efficiently and accurately. Multiple works by our group, and confirmed by others, have highlighted the value of 4D Flow MRI for evaluating this patient population, and for vascular imaging applications beyond the heart.

Gadopiclenol is a recently FDA-approved intravenous, extracellular gadolinium contrast agent indicated for use in MRI. Though it has been shown to be effective in detection of central nervous system (CNS) lesions and of lesions outside the CNS, its performance in cardiovascular imaging is unknown, particularly in cardiac MRI performed for evaluation of adult congenital heart disease. We therefore seek to evaluate whether use of gadopiclenol results in superior image quality compared to, and therefore may be used in place of, gadobenate dimeglumine, our current standard of care in 4D Flow MRI and MR Angiography (MRA).

In our current clinical practice, like many others, gadobenate dimeglumine at 0.3 mL/kg (0.15 mmol/kg) is our standard of care for vascular enhancement and cardiac MRI, favored due to its long blood pool residence time, which parallels the longer acquisition time for 4D Flow MRI (\~10 minutes), and its strong T1 shortening properties. Gadopiclenol, with its stronger T1 shortening properties and similar pharmacokinetics, may achieve similar effects but as a macrocyclic agent is a more stable gadolinium agent, and theoretically may have a better retention profile than older linear agents due to its lower approved dose. We therefore seek to determine whether gadopiclenol may be used in place of gadobenate dimeglumine for contrast-enhanced 4D Flow MRI and MRA. Since the optimal dose of gadopiclenol for this purpose is unknown, we will assess the relative performance of gadopiclenol across a dose range.

Standard dosing for gadopiclenol for CNS and abdominal imaging in adult and pediatric patients is 0.05 mmol/kg actual body weight (equivalent to 0.1 mL/kg). However, its safety has been evaluated at doses ranging from 0.025 mmol/kg to 0.3 mmol/kg. We therefore plan to assess the signal to noise ratio and image quality of patients undergoing cardiac MRI using gadopiclenol at three doses (0.075 mmol/kg, 0.10 mmol/kg, 0.15 mmol/kg) against our standard of care (gadobenate dimeglumine at 0.3 mL/kg (0.15 mmol/kg)). We hypothesize that gadopiclenol at each dose will be non-inferior to gadobenate dimeglumine, achieving similar qualitative image quality, similar SNR, and similar standard deviation amongst flow measurements with 4D Flow MRI. There is a strong possibility that gadopiclenol at an equimolar gadolinium dose to gadobenate dimeglumine will provide superior qualitative image quality and superior SNR in contrast-enhanced MRA and reduce standard deviation amongst flow measurements with 4D Flow MRI.

Eligibility criteria: Inclusion Criteria:

* Adult patients (≥ 18 years old)
* History of congenital heart disease and scheduled to undergo standard of care cardiac MRI and chest MRA as part of routine clinical care
* English is patient's primary spoken language

Exclusion Criteria:

* Pediatric patients
* Pregnant patients
* Patients with ongoing acute kidney injury (AKI) or severe, chronic kidney disease (GFR \< 30 mL/min/1.73m2)
* History of hypersensitivity reaction to gadolinium based contrast agent
* English is not the patient's primary spoken language

Primary outcomes:
measure: Image Quality
timeFrame: Image Quality will be assessed on a rolling basis during the study by all radiologists and will be completed within one month of the conclusion of enrollment.
measure: Signal-to-Noise Ratio (SNR)
timeFrame: SNR will be assessed on a rolling basis during the study by the study team and will be completed within one month of the conclusion of enrollment.
measure: Standard Deviation of Volumetric Flow Measurements
timeFrame: Standard deviation of flow measurements will be assessed on a rolling basis during the study by all attending radiologists and will be completed within one month after the conclusion of enrollment.
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California San Diego Health
state: California
Study officials:
affiliation: Department of Radiology, UC San Diego
name: Albert Hsiao, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jacobs K, Hahn L, Horowitz M, Kligerman S, Vasanawala S, Hsiao A. Hemodynamic Assessment of Structural Heart Disease Using 4D Flow MRI: How We Do It. AJR Am J Roentgenol. 2021 Dec;217(6):1322-1332. doi: 10.2214/AJR.21.25978. Epub 2021 Jun 2.
citation: Kebebew E, Tresler PA, Siperstein AE, Duh QY, Clark OH. Normal thyroid pathology in patients undergoing thyroidectomy for finding a RETgene germline mutation: a report of three cases and review of the literature. Thyroid. 1999 Feb;9(2):127-31. doi: 10.1089/thy.1999.9.127.
citation: Hsiao A, Alley MT, Massaband P, Herfkens RJ, Chan FP, Vasanawala SS. Improved cardiovascular flow quantification with time-resolved volumetric phase-contrast MRI. Pediatr Radiol. 2011 Jun;41(6):711-20. doi: 10.1007/s00247-010-1932-z. Epub 2011 Jan 11.