Clinical trial NCT04840225: Anemia in Patients With Endocarditis
Official title: Anæmi Hos Patienter Med infektiøs Endokarditis - Karakteristik og Mekanismer (ANIE)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Anemia
Endocarditis, Bacterial
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2021-04-09
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Prevalence of anemia during hospitalization
timeFrame: From time of diagnosis/intervention untill end of follow-up (up to 6 months from inclusion)
Secondary outcomes:
measure: Prevalence of iron deficiency anemia in patients with IE and relevant controls
timeFrame: From time of diagnosis/intervention untill end of follow-up (up to 6 months from inclusion)
measure: Prevalence of anemia due to inflammation in patients with IE and relevant controls
timeFrame: From time of diagnosis/intervention untill end of follow-up (up to 6 months from inclusion)
measure: Time untill resolution of inflammation and anemia in patients with IE and relevant controls
timeFrame: From time of diagnosis/intervention untill end of follow-up (up to 6 months from inclusion)
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
Study officials:
References: