急性心不全および鉄欠乏症患者における鉄デリソマルトースが運動能力と生活の質に及ぼす影響(COREVIVE-HFrEF) (COREVIVE-HFrEF)

Iron to be administered as ferric derisomaltose.

The treatment dose (mL) to be administered will be determined by the patient's body weight and hemoglobin (Hb) value.

Where Hb ≥10 g/dL, dosage according to body weight is as follows:

Body weight <50 kg: 20 mg/kg; Body weight 50 to <70 kg: 1000 mg; Body weight ≥70 kg: 20 mg/kg up to a maximum of 1500 mg.

Where Hb <10 g/dL, dosage according to body weight is as follows:

Body weight <50 kg: 20 mg/kg; Body weight 50 to <70 kg: 20 mg/kg; Body weight ≥70 kg: 20 mg/kg up to a maximum of 2000 mg.

Infused over a minimum of 15mins for doses up to and including 1000mg, and a minimum of 30 mins for doses >1000mg

After baseline assessments patients will be randomised in a 1:1 ratio to receive ferric derisomaltose IV or placebo (normal saline). In the Treatment group, Ferric derisomaltose will be administered according to the dosing schedule.

• モノファー
• 鉄(III)イソマルトシド 1000

Participants in this arm will receive normal saline 0.9% in analogy to treatment arm.

In the placebo group, patients will receive the equivalent number of normal saline injections.

• 生理食塩水

The difference of 6-minute walking distance in meters from baseline to day3 after IV iron injection.

The difference of 6-minute walking distance in meters from baseline at 2 weeks, 4weeks after IV iron injection.

KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. KCCQ-clinical summary score was average of domains- physical limitation and total symptoms (average of symptom frequency and symptom burden), and transformed to a single score which ranged from 0 (worst) -100 (the best possible status), where the higher score reflected better health status.

EQ-5D-5L: European Quality of Life-5 Dimensions-5 Levels The EQ 5D questionnaire consists of a health descriptive system for participants to self-classify and rate their health status on the day of administration.

The descriptive system includes 5 items/dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, which are coded from 1 (best state) to 5 (worst state).

NYHA = New York Heart Association

NYHA functional class was assessed as Class I, II, III, IV:

Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc.

Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity.

Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity. Comfortable only at rest.

Class IV - Severe limitations. Experiences symptoms even while at rest.

Lower response categories are better for score NYHA.

PGA:Patient Global Assessment

PGA questionnaire consists of a health descriptive system for participants to self-reported and rate their medical condition after participate this study.

The descriptive system includes 7 choices：has much improved, has (moderately) improved, has a little improved, is unchanged, is a little worse, is (moderately) worse, is much worse, which are coded from 1 (best state) to 7 (worst state).

Hemoglobin (Hb) is a commonly used clinical test for assessing anaemia, with units of g/L.

The reticulocyte ratio is often used to reflect the hematopoiesis of the bone marrow erythrocyte with units of percentage(%).

To assess the effect of ferric derisomaltose vs. placebo on change in ferritin from baseline to 3 days, 2weeks and 4weeks

To assess the effect of ferric derisomaltose vs. placebo on change in transferrin saturation from baseline to 3 days, 2weeks and 4weeks

To assess the effect of ferric derisomaltose vs. placebo on change in serum transferrin receptors (sTfR) from baseline to 3 days, 2weeks and 4weeks

To assess the effect of ferric derisomaltose vs. placebo on change in NT-proBNP from baseline to 3 days, 2weeks and 4weeks

Left ventricular ejection fraction is assessed by two-dimensional directed M-mode echocardiography.

Left ventricular end-diastolic diameter is assessed by two-dimensional directed M-mode echocardiography.

Urine Albumin-to-Creatinine Ratio (UACR) is regard as a safety endpoint to reflect early injury of kidney.

Safety endpoint is defined as a rise of high-sensitivity C-reaction protein (hs-CRP) from baseline.

Adverse Event Include Fishbane symptoms (flushing/chest pain/back pain/chest tightness, sometimes with dyspnea), isolated signs and symptoms (urticaria/pruritus/rash/mild hypotension, hypertension/tachycardia/nausea/headache), signs and symptoms of allergic reactions (persistent hypotension; airway angioedema/generalised urticaria, non-airway angioedema/wheezing, bronchospasm, vomiting, abdominal pain, etc.)