Next-generation, Integrative, and Personalized Risk Assessment to Prevent Recurrent Heart Failure Events: the ORACLE Study (ORACLE)

The aim of this study is to develop and validate an improved, comprehensive risk assessment algorithm integrating blood RNA-based biomarkers, clinical, and patient-centered data and to assess the incremental predictive value (discrimination and reclassification) compared to a traditional risk model (change in the c-statistics for prediction of the primary endpoint).

Study Overview

• Status: Recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Diagnostic test: Comprehensive risk assessment algorithm

Detailed Description

The ORACLE study is a multicenter, observational, prospective, cross-sectional and longitudinal study integrated by 3 different cohorts for 1) RNA biomarker discovery (60 nested case-control sample), 2) model derivation (516 nested case-control sample) and 3) external validation (new prospective cohort of 558 consecutive patients recruited in 4 hospital centers) according to a TRIPOD Statement type 3 analysis. In total 1134 consecutive patients with a HF hospitalization or urgent HF visit < 30 days before inclusion and followed for 6 months will be studied.

This study include the discovery of novel RNA-based biomarkers using next-generation sequencing technology to define and validate a new biomarker set and clinical and patient-centered risk determinants definition. A new model will be constructed; training and internal validation in the derivation cohort using machine learning methods, and finally an external validation of the new next generation integrative risk assessment model will be performed.

• Study Type: Observational
• Enrollment (Anticipated): 1134

Contacts and Locations

• Study Contact: Name: Josep Comín Colet, MD, PhD; Phone Number: +34 932607078; Email: jcomin@bellvitgehospital.cat
• Study Contact Backup: Name: Raúl Ramos Polo, MD; Phone Number: +34 932607078; Email: rramosp@bellvitgehospital.cat

Study Locations

• Spain
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • University Hospital Bellvitge
      • Contact: Josep Comín Colet, MD, PhD; Phone Number: 2274 +34-933-35-70-11; Email: jcomin@bellvitgehospital.cat
      • Contact: Raúl Ramos Polo, MD; Phone Number: 2274 +34-933-35-70-11; Email: rramosp@bellvitgehospital.cat

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The external validation cohort will be a multicenter, observational, prospective, cross-sectional and longitudinal cohort recruited for the specific purpose of the ORACLE study. The investigators plan to recruit patients with a recent (<30 days) acute HF event and follow them for 180 days. The study will be conducted in 4 different hospitals (University Hospital Bellvitge, Viladecans General Hospital, Vic General Hospital and Igualada General Hospital) covering a total healthcare area of > 650.000 inhabitants.

Description

Inclusion Criteria:

• Age ≥ 18 years old.
• Patients with a recent (<30 days) acute decompensation of HF requiring intravenous diuretic therapy (either hospitalized or in ambulatory care) or intensification of oral diuretics (ambulatory care).
• HF diagnosis according to European Society of Cardiology (ESC) criteria.
• Written informed consent
• Patients receiving oral standard medication for chronic HF.

Exclusion Criteria:

• Age<18 years old.
• Death before hospital discharge.
• The patient is unable or unwilling to give the informed consent to participate.
• Unstable patients with signs of fluid overload or low cardiac output at the moment of enrollment.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the model performance of the comprehensive risk assessment algorithm with a traditional risk model to predict HF related hospitalizations or all-cause death	To compare in an external validation cohort of patients a recent acute HF event, the performance (discrimination, additive predictive value, and reclassification ability) of a comprehensive risk assessment algorithm with the performance of a traditional risk model to predict the occurrence of the primary composite clinical end-point of HF related hospitalizations (readmissions) or all-cause death at 180 days after hospital discharge or after an urgent HF visit (acute HF event requiring intravenous administration of diuretics without admission).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the model performance of the comprehensive risk assessment algorithm with a traditional risk model to predict the occurrence of HF-related hospitalizations (readmissions) or all-cause death at 30, and 90 days after hospital discharge.	The admission will be considered as HF-related if it suits with one of the following conditions: Cardiovascular cause hospitalization; Complication directly related with prior HF admission; Decompensation of prior disease or comorbidity	6 months
To compare the model performance of the comprehensive risk assessment algorithm with a traditional risk model to predict the occurrence of HF-related hospitalizations (readmissions) at 30, 90, and 180 days after hospital discharge.		6 months
To compare the model performance of the comprehensive risk assessment algorithm with a traditional risk model to predict the occurrence of all-cause death at 30, 90, and 180 days, after hospital discharge.		6 months

Other Outcome Measures

Outcome Measure	Time Frame
Explore the performance (sensibility and specificity) of the developed model according gender, LVEF (preserved or reduced left ventricle ejection fraction), comorbidity burden (Charlson Comorbidity Index) and frailty.	6 months

Collaborators and Investigators

• Sponsor: Hospital Universitari de Bellvitge

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2022
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: January 8, 2023
• First Posted (Estimate): January 11, 2023

Study Record Updates

• Last Update Posted (Estimate): January 11, 2023
• Last Update Submitted That Met QC Criteria: January 8, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Machine Learning; Outcomes Research; Multi-Omics Approaches; Patient-Centered Information
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: PI21/00264

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