Anemia in Patients With Endocarditis (ANIE)

Anæmi Hos Patienter Med infektiøs Endokarditis - Karakteristik og Mekanismer (ANIE)

Prospective study of prevalence and deep charecterization of anemia in patients with endocarditis from diagnosis undtill 6 months after discharge.

Study Overview

• Status: Recruiting
• Conditions: Anemia; Endocarditis, Bacterial
• Intervention / Treatment: Other: Measurement of biomarkers for inflammation and anemia

Detailed Description

Anemia is an adverse prognostic marker in both cardiac diseases and infectious diseases. In patients with bacterial endocarditis (IE), anemia has a prevalence of 55-80%. In a sub-study to our POET I trial (RCT with 400 patients with IE, published in NEJM 2019), preliminary data show a 5-fold increased risk of death within 6 months and 2-fold increased risk after 3 years, in non-surgically treated patients with hemoglobin <6.2mmol/L, compared to patients with no or mild anemia. Intensified treatment of anemia through e.g. intravenous iron infusions, in combination with erythrocyte stimulating agents or new treatments for anemia of inflammation, such as IL-6 inhibitors, could possibly improve outcome for patients with IE.

This study - ANIE - is a prospective study, aiming at further deep-characterizing of anemia in patients with IE, and associated outcomes. Degree of anemia of inflammation (AI) and iron-deficiency anemia during hospitalization and time to recovery will be assessed. Blood samples from 100 patients with IE will be collected during hospitalization and 3 months after discharge, i.e. also during expected recovery. Samples will be analyzed for standard markers of anemia and inflammation, as well as novel biomarkers for AI, such as IL-6, soluble transferrin receptor, erythroferrone and hepcidin. The sample size calculation is based on the assumption that the prevalence of AI is 50%, with a confidence interval of 95% and a margin of error of <10%. Comparisons will be made to patients with other infections and patients with pure inflammation (TAVI and TEVAR patients) and healthy blood donors.

ANIE is expected to give us an unprecedented insight into disease processes, stages and possible therapeutic targets for anemia in patients with IE.

The results will serve for designing the clinical trial of novel interventions to treat anemia in patients with IE, as a novel means to improve the outcome and reduce the high mortality in these patients.

Anemia is an adverse prognostic marker in both cardiac diseases and infectious diseases. In patients with bacterial endocarditis (IE), anemia has a prevalence of 55-80%. In a sub-study to our POET I trial (RCT with 400 patients with IE, published in NEJM 2019), preliminary data show a 5-fold increased risk of death within 6 months and 2-fold increased risk after 3 years, in non-surgically treated patients with hemoglobin <6.2mmol/L, compared to patients with no or mild anemia. Intensified treatment of anemia through e.g. intravenous iron infusions, in combination with erythrocyte stimulating agents or new treatments for anemia of inflammation, such as IL-6 inhibitors, could possibly improve outcome for patients with IE.

This study - ANIE - is a prospective study, aiming at further deep-characterizing of anemia in patients with IE, and associated outcomes. Degree of anemia of inflammation (AI) and iron-deficiency anemia during hospitalization and time to recovery will be assessed. Blood samples from 100 patients with IE will be collected during hospitalization and 3 months after discharge, i.e. also during expected recovery. Samples will be analyzed for standard markers of anemia and inflammation, as well as novel biomarkers for AI, such as IL-6, soluble transferrin receptor, erythroferrone and hepcidin. The sample size calculation is based on the assumption that the prevalence of AI is 50%, with a confidence interval of 95% and a margin of error of <10%. Comparisons will be made to patients with other infections and patients with pure inflammation (TAVI and TEVAR patients) and healthy blood donors.

ANIE is expected to give us an unprecedented insight into disease processes, stages and possible therapeutic targets for anemia in patients with IE.

The results will serve for designing the clinical trial of novel interventions to treat anemia in patients with IE, as a novel means to improve the outcome and reduce the high mortality in these patients.

• Study Type: Observational
• Enrollment (Anticipated): 190

Contacts and Locations

• Study Contact: Name: Mia Marie Pries-Heje, MD; Phone Number: +45 35454245; Email: mia.marie.pries-heje.01@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
    • Contact: Mia Marie Pries-Heje; Phone Number: +4535454245

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

100 patients with IE, 30 undergoing elective TAVI/TECAR, 30 with non-IE bacterial infections and 30 healthy blood donors

Description

IE-patients:

Inclusion Criteria:

• Infectious endocarditis, defined by Duke criteria

Exclusion Criteria:

• Known rheumatic disease or immune defect

TAVI/TEVAR patients:

Inclusion Criteria:

• Scheduled for a TAVI/TEVAR procedure

Exclusion criteria:

• Clinical suspicion of infection
• Known rheumatic disease or immune defect

Bacterial patients without IE (short infection):

Inclusion criteria

• Patients admitted with an infection with gram positive bacteria, without IE Exclusion criteria
• Known rheumatic disease or immune defect

Blood donors:

Exclusion criteria:

• Antibiotic treatment within the last 2 months
• Cancer, rheumatic disease or other known inflammatory disease
• Surgery within the last 3 months
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Endocarditis; 100 patients diagnosed with infectious endocarditis according to DUKE criteria. Detailed characterization of inflammation, anemia and markers of iron hemostatis will be made at diagnosis and followed undtill 6 months after discharge.	Other: Measurement of biomarkers for inflammation and anemia; Measurement of biomarkers for inflammation and anemia, in addition to standart clinical measurements
TAVI/TEVAR patietns; 30 patients undergoing elektive TAVI/TEVAR procedures. Detailed characterization of inflammation, anemia and markers of iron hemostatis will be made at directly prior to procedure and followed undtill 3 months after discharge.	Other: Measurement of biomarkers for inflammation and anemia; Measurement of biomarkers for inflammation and anemia, in addition to standart clinical measurements
Patients with bacterial infections without endocarditis; 30 patients diagnosed with with bacterial infections, without endocarditis. Detailed characterization of inflammation, anemia and markers of iron hemostatis will be made at diagnosis and followed undtill 3 months after discharge.	Other: Measurement of biomarkers for inflammation and anemia; Measurement of biomarkers for inflammation and anemia, in addition to standart clinical measurements
Healthy blood donors; Detailed characterization of inflammation, anemia and markers of iron hemostatis will be made at directly prior to blood donation and approximately 1 week after blood donations	Other: Measurement of biomarkers for inflammation and anemia; Measurement of biomarkers for inflammation and anemia, in addition to standart clinical measurements

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of anemia during hospitalization	Diagnosis of anemia through WHO/NCI criteria for anemia and severity of anemia at time of diagnosis, 1-4 weeks after initiation of relevant treatment and up to 6 months after discharge	From time of diagnosis/intervention untill end of follow-up (up to 6 months from inclusion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of iron deficiency anemia in patients with IE and relevant controls	Determination of the prevalence of iron deficiency anemia through measurements of hemoglobin, markers of anemia and of iron metabolism/stores in blood	From time of diagnosis/intervention untill end of follow-up (up to 6 months from inclusion)
Prevalence of anemia due to inflammation in patients with IE and relevant controls	Determination of the prevalence of anemia og inflammation through measurements of markers of anemia of inflammation (IL-6 hepcidin, erytroferrone, soluble transferrin receptor)	From time of diagnosis/intervention untill end of follow-up (up to 6 months from inclusion)
Time untill resolution of inflammation and anemia in patients with IE and relevant controls	Determination of time from start of treatment/intervention until normalization of markers of inflammation and anemia, as well as normalization of erythropoiesis	From time of diagnosis/intervention untill end of follow-up (up to 6 months from inclusion)

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2021
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: March 29, 2021
• First Submitted That Met QC Criteria: April 8, 2021
• First Posted (Actual): April 9, 2021

Study Record Updates

• Last Update Posted (Actual): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 25, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Infections; Hematologic Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Cardiovascular Infections; Anemia; Endocarditis, Bacterial; Endocarditis
• Other Study ID Numbers: H-20044379

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Available on reasonable request

Drug and device information, study documents

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