Effect of Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation

Iron-deficiency Clinical Trial

— EFFECT-KTx  

Official title:

Effect of Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation: a Multicenter Randomized Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03769441
• Other study ID #: 201800450
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 2, 2019
• Est. completion date: September 1, 2024

Study information

• Verified date: February 2024
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Iron deficiency is common in kidney transplant recipients and is associated with impaired exercise tolerance and an unfavourable prognosis.

This multicentre double-blind, placebo-controlled randomized controlled clinical trial will allow the investigators to analyse the effects of intravenous iron correction with ferric(III) carboxymaltose on exercise tolerance and other parameters, in comparison to a placebo.

Description:

Rationale: Iron deficiency is common in kidney transplant recipients. The presence of iron deficiency is associated with an unfavourable prognosis in these patients. In patients with heart failure and iron deficiency, treatment with intravenous iron improved exercise capacity and quality of life. Whether such beneficial effects may also occur in kidney transplant recipients is unknown.

Objective: Our main objective is to address whether correction of iron deficiency with ferric(III) carboxymaltose improves exercise tolerance and quality of life in iron-deficient kidney-transplant recipients.

Study design: A multicentre double-blind, placebo-controlled randomized controlled clinical trial will be performed to compare the effects of ferric(III) carboxymaltose with placebo.

Study population: 158 iron-deficient kidney transplant recipients. The intervention arm will receive 10 mL of ferric(III) carboxymaltose (50 mg Fe3/mL, intravenously) every six weeks, with a total of four dosages. The control arm receives an intravenous placebo solution (saline).

Main study parameters/endpoints: The primary endpoint is the distance walked in six minutes, as quantified by the six-minute-walking-test at the end of follow-up.

The investigators expect that iron-deficient kidney transplant recipients will benefit from ferric(III) carboxymaltose treatment as a result of an improvement in exercise tolerance and general wellbeing.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 148
• Est. completion date: September 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Kidney transplant recipient

• Iron deficiency, defined by a ferritin level of =100 ug/L, or 100-299 ug/L combined with a transferrin saturation of =20%

• At least six months after transplantation at baseline

• Age =18 years

• Ability to comply with the study protocol

• Informed consent

Exclusion Criteria:

• Intolerance to any intravenous iron solution

• Severe anemia (Hb <10.5 g/dL, <6.5 mmol/L), microcytic anemia (MCV <80 fl) or progressive anemia (?3.2 g/dL per month decline for two months or more)

• A positive feces occult blood test or otherwise demonstrated gastrointestinal, or urogenital, blood loss

• Blood transfusion in the past six weeks

• Polycythemia (Hb >15.3 g/dL, 9.5 mmol/L)

• Estimated glomerular filtration rate (eGFR) of = 30 ml/min per 1.73 m2

• History of haemochromatosis

• Unstable angina or myocardial infarction during the previous month

• Disability to walk

• Severe hypophosphatemia in the month before baseline (serum phosphate <0.35 mmol/L)

• Pregnancy or inability to take adequate contraceptive measures when at childbearing age (women)

• Any signs of an active systemic infection

• Participation in another interventional study

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Iron-deficiency
• Transplant-Related Disorder

Intervention

Drug:
• Ferric carboxymaltose
Four intravenous dosages of ferric(III) carboxymaltose
• Sodium chloride
Four intravenous dosages of sodiumchloride

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen
Netherlands	University Medical Center Utrecht	Utrecht

Sponsors (3)

Lead Sponsor	Collaborator
University Medical Center Groningen	Dutch Kidney Foundation, Vifor Fresenius Medical Care Renal Pharma

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exercise tolerance	The between-group difference in change in exercise tolerance quantified by the six-minute walk test (6MWT)	24 weeks
Secondary	Hemoglobin level	The between-group difference in change in hemoglobin level	24 weeks
Secondary	Iron status	The between-group difference in change in iron parameters (plasma iron, ferritin, transferrin saturation)	24 weeks
Secondary	Cardiac function	The between-group difference in change in cardiac structure, function and strain, analysed with a transthoracic echocardiography	24 weeks
Secondary	Muscle strength 1	The between-group difference in change in muscle strength measured by the 'Five-Times-Sit-to-Stand-test (FTSTS)	24 weeks
Secondary	Muscle strength 2	The between-group difference in change in muscle strength measured by the timed-up-and-Go test (TUG)	24 weeks
Secondary	Muscle strength 3	The between-group difference in change in muscle strength measured by handgrip dynamometry	24 weeks
Secondary	Muscle mass	The between-group difference in change in muscle mass assessed using 24-hour urinary creatinine excretion	24 weeks
Secondary	Phosphate level	The between-group difference in change in phosphate level	24 weeks
Secondary	Calcium level	The between-group difference in change in calcium level	24 weeks
Secondary	Vitamin D status	The between-group difference in change in vitamin D level	24 weeks
Secondary	Parathyroid hormone	The between-group difference in change in parathyroid hormone level level	24 weeks
Secondary	FGF23	The between-group difference in change in FGF23 level	24 weeks
Secondary	Intestinal microbiota	The between-group difference in change in intestinal microbiota	24 weeks
Secondary	Incidence of any infection	The between-group difference in incidence of infections	24 weeks
Secondary	Incidence of hospitalisation	The between-group difference in incidence of hospitalisation	24 weeks
Secondary	Incidence of cardiac events	The between-group difference in incidence of cardiac events	24 weeks
Secondary	Incidence of graft failure	The between-group difference in incidence of graft failure	24 weeks
Secondary	Lymphocyte production of cytokines	The between-group difference in lymphocyte cytokine espression (measured with facs)	24 weeks
Secondary	Lymphocyte production of immunoglobulins	The between-group difference in lymphocyte IgG production (measured with ELISA)	24 weeks
Secondary	Lymphocyte proliferation rate	The between-group difference in lymphocyte proliferation rate (assessed with FACS)	24 weeks
Secondary	B-lymphocyte differentiation rate	The between-group difference in B-lymphocyte plasma cell formation (assessed with Facs)	24 weeks
Secondary	Cognitive performance (memory span)	The between-group difference in change in cognitive performance quantified with neuropsychological testing (Digit Span Forward Test, minimum value 0, maximum value 9, a higher score means a better outcome)	24 weeks
Secondary	Cognitive performance (verbal memory)	The between-group difference in change in cognitive performance quantified with neuropsychological testing (15 word test, minimum value 0, maximum value 75, a higher score means a better outcome)	24 weeks
Secondary	Cognitive performance (semantic memory)	The between-group difference in change in cognitive performance quantified with neuropsychological testing (Word Fluency Test, minimum value 0, no maximum value, a higher score means a better outcome)	24 weeks
Secondary	Cognitive performance (processing speed)	The between-group difference in change in cognitive performance quantified with neuropsychological testing (symbol digit modalities test, minimum value 0, maximum value 110, a higher score means a better outcome)	24 weeks
Secondary	Cognitive performance (visuomotor and mental speed)	The between-group difference in change in cognitive performance quantified with neuropsychological testing (Trail Making Test A, minimum value 1, no maximum value, a lower score means a better outcome)	24 weeks
Secondary	Cognitive performance (cognitive flexibility)	The between-group difference in change in cognitive performance quantified with neuropsychological testing (Trail Making Test B, minimum value 1, no maximum value, a lower score means a better outcome)	24 weeks
Secondary	Cognitive performance (executive control)	The between-group difference in change in cognitive performance quantified with neuropsychological testing (Controlled Oral Word Association Test, minimum score 1, no maximum score, a higher score means a better outcome)	24 weeks
Secondary	Cognitive performance (working memory)	The between-group difference in change in cognitive performance quantified with neuropsychological testing (Digit Span Backward, minimum score 0, maximum score 8, a higher score means a better outcome)	24 weeks
Secondary	Plasma creatinine	The between-group difference in change in plasma creatinine	24 weeks
Secondary	Quality of Life (health)	The between-group difference in change in quality of life quantified with SF36 questionnaire. A higher score means a better outcome.	24 weeks
Secondary	Quality of Life (subjective fatigue)	The between-group difference in change in quality of life quantified with the Dutch Checklist individual Strength). A higher score means worse fatigue.	24 weeks
Secondary	Quality of Life (long-lasting fatigue)	The between-group difference in change in quality of life quantified with the Dutch Multifactor Fatigue Scale). A higher score means worse fatigue.	24 weeks
Secondary	Quality of Life (overall)	The between-group difference in change in quality of life quantified with EuroQol-5D-5L	24 weeks
Secondary	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination IgG response	The between-group difference in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specific antibody titre after vaccination.	12 months
Secondary	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination T-lymphocyte response	The between-group difference in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specif T-lymphocyte response after vaccination.	12 months
Secondary	Gastro-intestinal symptoms	The between-group difference in change in gastro-intestinal symptoms assessed with the gastrointestinal symptom rating scale.	24 weeks
Secondary	Hepatic injury	The between-group difference in change in plasma hepatic enzyme levels (aspartate transaminase and alanine transaminase)	24 weeks
Secondary	Restless legs	The between-group difference in prevalence of restless legs symptoms before and after treatment	24 weeks
Secondary	Kidney graft rejection and injury	The between-group difference in change in urine kidney injury marker levels	24 weeks