Clinical trial NCT06903559: Roxadustat's Effect on Heart, Nutrition, and Inflammation in Hemodialysis Patients
Official title: Effect of Roxadustat on Cardiovascular System and Malnutrition-Inflammation-Atherosclerosis (MIA) Syndrome in Hemodialysis Patients: A Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Kidney Failure, Chronic
Malnutrition-Inflammation Syndrome
Anemia in End Stage Renal Disease
Cardiovascular Diseases (CVD)
Keywords: Roxadustat
Hemodialysis
Renal Anemia
Cardiovascular Diseases
Malnutrition-Inflammation-Atherosclerosis Syndrome
Lead sponsor: Mansoura University
Sponsor class: OTHER
First posted: 2025-03-30
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients with kidney failure who require hemodialysis often suffer from anemia (low red blood cell count), heart and blood vessel problems, and a condition involving poor nutrition, inflammation, and hardening of the arteries (called MIA syndrome). Standard treatments for anemia often involve injections and iron supplements. This study aims to see if a newer oral medication, Roxadustat, works better than these standard treatments not only for anemia but also for improving cardiovascular health and the MIA syndrome.

Participants in the study will be randomly assigned (like by chance) to one of two groups. One group will receive Roxadustat, while the other group will continue with their conventional anemia treatment. Researchers will compare the effects on heart function, markers of nutrition and inflammation, and anemia levels in both groups over a 6-month period.

Detailed description: Renal anemia is a frequent and significant complication in patients with end-stage kidney disease undergoing hemodialysis, affecting over 90% of this population. Anemia adversely impacts quality of life and is associated with increased cardiovascular risk, hospitalization rates, and mortality. These patients also commonly experience Malnutrition-Inflammation-Atherosclerosis (MIA) syndrome and have significantly elevated cardiovascular mortality compared to the general population. While Erythropoiesis-stimulating agents (ESAs) are a mainstay of therapy, concerns exist regarding potential adverse events, particularly with high doses, highlighting the need for alternative or complementary strategies.

Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that represents a newer class of agents for treating renal anemia. By inhibiting HIF degradation, Roxadustat mimics a hypoxic state, leading to enhanced endogenous erythropoietin synthesis and improved iron metabolism pathways. While its efficacy in managing anemia is established, its potential effects on the interconnected issues of cardiovascular disease (CVD) and MIA syndrome in the hemodialysis population remain poorly understood and require further investigation.

This study hypothesizes that Roxadustat, compared to conventional anemia management, may offer benefits beyond hemoglobin correction, potentially improving cardiovascular parameters and ameliorating aspects of the MIA syndrome in hemodialysis patients.

This is a randomized, open-label, parallel-group, controlled clinical trial conducted at the Urology and Nephrology center, Mansoura University. Eligible chronic hemodialysis patients will be randomized 1:1 to receive either Roxadustat (intervention group) or continue conventional anemia therapy (control group) for a duration of 6 months. Conventional therapy typically includes ESAs and iron supplementation as per standard clinical practice.

Key assessments will include evaluation of cardiovascular status (utilizing echocardiography for structural and functional assessment, and Doppler ultrasound for carotid intima-media thickness), markers relevant to MIA syndrome (including anthropometric measurements, inflammatory markers like high-sensitivity C-reactive protein (hs-CRP) and Endothelin-1, nutritional markers, lipid profiles, and measures like normalized protein catabolic rate (nPCR)), and parameters related to anemia management (hemoglobin, iron indices). Data will be collected at baseline and at the end of the 6-month study period. Safety monitoring will occur throughout the trial. Statistical analysis will compare changes between the two groups using appropriate methods for quantitative and qualitative data.

Eligibility criteria: Inclusion Criteria:

* Age of patient is more than 18.
* Patients who are willing to sign informed consent.
* Patients with ESKD on chronic hemodialysis for more than 3 months.

Exclusion Criteria:

* Current pregnancy or lactation.
* Patients with pre-existing malignancy.
* Patients with psychosis or on hypnotics.
* Refuse to participate in the study.
* Known history of hematological disorders or other known causes for anemia other than CKD or dialysis.
* Patients with severe cardiovascular disease

Primary outcomes:
measure: Change from Baseline in Left Ventricular Ejection Fraction (LVEF) at 6 Months
timeFrame: Baseline and 6 months
Secondary outcomes:
measure: Change from Baseline in Carotid Intima-Media Thickness (CIMT) at 6 Months
timeFrame: Baseline and 6 months
measure: Change from Baseline in High-Sensitivity C-Reactive Protein (hs-CRP) Level at 6 Months
timeFrame: Baseline and 6 months
measure: Change from Baseline in Normalized Protein Catabolic Rate (nPCR) at 6 Months
timeFrame: Baseline and 6 months
Other outcomes:
Locations:
city: Mansoura
country: Egypt
facility: Urology and Nephrology Center, Mansoura University
state: Dakahliya
Study officials:
References:
citation: Sanghani NS, Haase VH. Hypoxia-Inducible Factor Activators in Renal Anemia: Current Clinical Experience. Adv Chronic Kidney Dis. 2019 Jul;26(4):253-266. doi: 10.1053/j.ackd.2019.04.004.
citation: Yap DYH, McMahon LP, Hao CM, Hu N, Okada H, Suzuki Y, Kim SG, Lim SK, Vareesangthip K, Hung CC, Nangaku M; APSN HIF-PHI Recommendation Committee. Recommendations by the Asian Pacific society of nephrology (APSN) on the appropriate use of HIF-PH inhibitors. Nephrology (Carlton). 2021 Feb;26(2):105-118. doi: 10.1111/nep.13835. Epub 2020 Dec 9.
citation: Zhou Q, Mao M, Li J, Deng F. The efficacy and safety of roxadustat for anemia in patients with dialysis-dependent chronic kidney disease: a systematic review and meta-analysis. Ren Fail. 2023 Dec;45(1):2195011. doi: 10.1080/0886022X.2023.2195011.