EVAluation of Erythrocytosis PRospEctive Cohort STudy (EVEREST)

Evaluation of Erythrocytosis Prospective Cohort Study (EVEREST): Diagnosis, Management and Longitudinal Outcomes in Patients with Elevated Hemoglobin

The EValuation of ERythrocytosis pRospEctive cohort STudy (EVEREST) is a prospective study designed to shed light on these key questions in the diagnosis, management, and clinical outcomes in patients with elevated hemoglobin (erythrocytosis). This longitudinal, prospective study will generate high quality data that can help inform the optimal approach to diagnosis and management in this patient population.

Study Overview

• Status: Not yet recruiting
• Conditions: Polycythemia Vera; Polycythemia; Erythrocytosis; Polycythemia Vera (PV); Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase; Polycythemia Secondary; Polycythemia; Familial; Polycythemia, Primary

Detailed Description

The EVAluation of Erythrocytosis pRospEctive cohort STudy (EVEREST) is a prospective, longitudinal, observational study designed to provide insights into the diagnosis, management, and outcomes of patients with elevated hemoglobin (erythrocytosis). This study aims to address key gaps in understanding the underlying causes, diagnostic approaches, and clinical outcomes of patients presenting with erythrocytosis in real-world clinical settings.

Erythrocytosis, defined as an elevated hemoglobin concentration, is a frequent reason for referral to hematology and presents substantial diagnostic and therapeutic challenges. The condition may arise from primary causes, such as polycythemia vera (PV), or secondary causes, including chronic hypoxia, erythropoietin-secreting tumors, medications, and exogenous testosterone use. Despite advances in diagnostic tools, there remains considerable uncertainty about the most effective ways to evaluate and manage erythrocytosis, particularly in distinguishing secondary from primary causes and in mitigating associated risks such as arterial and venous thrombosis.

EVEREST is designed to address these knowledge gaps by enrolling a diverse cohort of patients referred to hematology for evaluation of erythrocytosis. Participants will undergo comprehensive clinical evaluation and assessment of potential underlying causes. Data will be collected longitudinally to evaluate real-world management practices, such as the use of phlebotomy, cytoreductive therapy, and antithrombotic agents, and to document clinical outcomes, including rates of thrombosis, bleeding, disease progression, and mortality.

The study has four main objectives:

1. To prospectively measure the incidence of various causes of erythrocytosis in patients referred for elevated hemoglobin levels.
2. To prospectively evaluate the diagnostic accuracy of the JAKPOT prediction rule, a simple prediction rule using complete blood count parameters, for identifying JAK2-positive erythrocytosis/polycythemia vera and differentiating it from secondary causes.
3. To evaluate real-world management strategies for patients with erythrocytosis.
4. To document longitudinal clinical outcomes, including thrombosis, bleeding, disease progression, and survival.

EVEREST aims to recruit 1,500 adult patients across participating clinics. Participants will be followed for clinical outcomes, and data will be collected to better characterize therapeutic approaches utilized in routine clinical care. This study seeks to generate evidence that will inform clinical practice and improve patient care for patients with erythrocytosis.

Outcome Measures EVEREST is a prospective observational study which will investigate multiple interrelated aspects of erythrocytosis, encompassing its causes, diagnostic evaluation, management strategies, and clinical outcomes. Two co-primary outcome measures have been selected to reflect the study's main objectives to measure the incidence and causes of erythrocytosis and the diagnostic accuracy of the JAKPOT prediction rule. Additionally, secondary outcome measures will focus on real-world management strategies and longitudinal clinical outcomes, providing further insights to inform patient care.

• Study Type: Observational
• Enrollment (Estimated): 1500

Contacts and Locations

• Study Contact: Name: Cyrus C. Hsia, MD, FRCPC; Phone Number: 56060 1-519-685-8500; Email: cyrus.hsia@lhsc.on.ca
• Study Contact Backup: Name: Benjamin Chin-Yee, MD, FRCPC; Phone Number: 1-519-685-8718; Email: benjamin.chin-yee@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Victoria Hospital, London Health Sciences Centre
      • Contact: Cyrus C. Hsia, MD, FRCPC; Phone Number: 56060 1-519-685-8500; Email: cyrus.hsia@lhsc.on.ca
      • Contact: Benjamin Chin-Yee, MD, FRCPC; Phone Number: 1-519-685-8718; Email: benjamin.chin-yee@lhsc.on.ca
      • Contact: Jenny Ho, MD, FRCPC
      • Contact: Alejandro Lazo-Langner, MD, FRCPC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

EVEREST will recruit adult patients evaluated for erythrocytosis, hemoglobin levels >=165 g/L in males or >=160 g/L in females, in hematology clinics at London Health Sciences Centre.

Description

Inclusion Criteria:

1. Adult patients (>=18 years) referred to hematology clinics at London Health Sciences Centre with hemoglobin levels >=165 g/L in males or >=160 g/L in females.
2. Patients capable of providing informed consent.
3. Age >= 18 years.

Exclusion Criteria:

1. Patients <18 years.
2. Patients without erythrocytosis.
3. Patients incapable of providing informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Erythrocytosis patients; Adult patients (>=18 years) referred to hematology clinics at London Health Sciences Centre (LHSC) with erythrocytosis or polycythemia with hemoglobin levels >=165 g/L in males or >=160 g/L in females at the time of initial clinic visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Causes of Erythrocytosis	The study will measure the incidence of primary and secondary causes of erythrocytosis, including polycythemia vera (PV), chronic hypoxia, medication use (e.g., SGLT2 inhibitors, testosterone), and other secondary causes. Data will be derived from clinical records and diagnostic investigations conducted as part of routine care. Unit of Measure: Proportion of participants (%) and count (n) categorized by cause over the study duration.	5 years
Diagnostic Accuracy of the JAKPOT Prediction Rule	The diagnostic accuracy of the JAKPOT prediction rule will be assessed for differentiating JAK2-positive erythrocytosis/PV from other causes. Measures will include sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Unit of Measure: Sensitivity (%), specificity (%), PPV (%), and NPV (%).	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Management Strategies	The study will document the proportion of participants receiving various management strategies, including phlebotomy, cytoreductive therapy, antiplatelet agents (e.g., aspirin), and anticoagulants. Data will include timing, frequency, and type of intervention, as recorded in clinical records. Unit of Measure: Proportion of participants (%) and count (n) receiving each management strategy.	5 years
Incidence of Thrombotic Events	Thrombotic events, including venous thromboembolism (deep vein thrombosis, pulmonary embolism) and arterial thrombosis (ischemic stroke, myocardial infarction), will be documented based on clinical records and imaging results. Standard definitions will be applied for classification. Unit of Measure: Events per 100 person-years.	5 years
Incidence of Bleeding Events	Bleeding events, categorized as major or clinically relevant non-major bleeding following ISTH definitions, will be measured. Data will include site, severity, and clinical consequences of bleeding. Unit of Measure: Events per 100 person-years.	5 years
Disease Progression	Disease progression, defined as transformation to myeloproliferative neoplasms (e.g., myelofibrosis, myelodysplastic syndrome, acute leukemia) or other hematologic malignancies, will be captured. Progression will be classified using WHO criteria and supported by clinical and laboratory data. Unit of Measure: Incidence per 100 person-years.	5 years
Mortality	Mortality data will include all-cause and cause-specific deaths, categorized as cardiovascular-related, thrombotic, hemorrhagic, or due to disease progression. Cause-specific data will be confirmed by clinical documentation or autopsy reports where available. Unit of Measure: Incidence per 100 person-years.	5 years

Collaborators and Investigators

• Sponsor: Cyrus Hsia

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: September 15, 2024
• First Submitted That Met QC Criteria: January 19, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 19, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Outcomes; Observational Study; Diagnosis; Management; Polycythemia; Prospective; Patient Registry; Erythrocytosis
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Polycythemia Vera; Polycythemia
• Other Study ID Numbers: HSREB125939

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No