Effect of Low Doses of Hypoxia-inducible Factor- Prolyl Hydroxylase Enzyme Inhibitor Plus Iron in the Treatment of Anemia in Dialysis-dependent Chronic Kidney Disease Patients

this study aims to :

1. To compare the efficacy of combining low doses of Roxadustat Hypoxia-Inducible Factor (HIF)-Prolyl Hydroxylase (PHD) inhibitor and iron versus standard treatment with erythropoietin-stimulating agents (ESA) in the treatment of anemia as a complication of chronic kidney disease (CKD) among dialysis-dependent patients.
2. To emphasize the safety profile of low doses of Roxadustat HIF-PHD.
3. To assess changes in the quality of life of patients with kidney disease before and after treatment.

Study Overview

• Status: Completed
• Conditions: Anemia in Dialysis-dependent CKD Patients
• Intervention / Treatment: Drug: Roxadustat

Detailed Description

1- The Ethics Committee of Alexandria University approved conducting the research in April 2023.

2. Informed consent will be obtained from all patients to participate in the trial after a thorough explanation of the nature of the study 3. Dialysis-dependent CKD patients with anemia will be recruited from Alexandria University Hospital &/or private hospitals (if any).

4. Study design: two-arm open-label non randomized active control study 5. Sample size was calculated using G*Power 3, a minimal total hypothesized sample size of 72 eligible adult Dialysis dependent CKD patients (DD -CKD) with anemia [ 36 per group] is needed; taking into consideration 95% confidence level, the effect size of 0.6. and 80% power using a t-test.

6. Three phases will comprise the trial: a screening phase that lasts from 2-4 weeks, a therapy phase that lasts for up to 12 weeks, and a follow-up phase that lasts 2-4 weeks. After obtaining informed consent, during visit 1, we will check the inclusion and exclusion criteria At each visit, the patient's well-being and the occurrence of any Drug-Related Adverse effects (DRAs) will be monitored accurately.

7. The Arabic-translated reliable and valid version of the Kidney Disease Quality of Life questionnaire (KDQOL-36) for patients with CKD will be completed with patients during the interview at the baseline and after fulfilling the whole study period 8. The collected data will be subjected to statistical analysis by the use of suitable techniques to achieve the objectives of the study

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt
    • Alexandria University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- 1. Ages >18. 2. End Stage Renal Disease (ESRD) on Incident Dialysis (ID), defined as dialysis ≥2 weeks but ≤4 months or stable dialysis (dialysis dependent DD) defined as dialysis for ≥ 4 months &having hemodialysis access.

3. Hb ≤10.5 g/dl during the screening period. 4. Erythropoiesis-stimulating agents (ESAs) naïve patients, ESAs resistant patients, or patients who didn't receive any ESA treatment within 4-6 weeks

Exclusion Criteria:

• 1. Age <18 year or >80 year 2. Known hypersensitivity to active substances, peanuts, soya, or any of the drug excipients.

  3. History of hereditary problems galactose intolerance 4. Systolic BP ≥160 mmHg or diastolic BP ≥95 mmHg, within 2 weeks prior to randomization. Patients may be reevaluated once BP is controlled.

  5. Congestive heart failure (CHF), New York Heart Association (NYHA) Class III or IV 6. Acute coronary syndrome (ACS), a thrombotic/thromboembolic event (eg, deep vein thrombosis (DVT) or pulmonary embolism (PE)), stroke, or seizure, within 12 weeks prior to randomization.

  7. Elective coronary revascularization or elective surgery that is expected to lead to significant blood loss.

  8. Hematologic diseases such as thalassemia, sickle cell anemia, active inflammatory bowel disease, active or chronic gastrointestinal bleeding, significant blood loss, or any other known causes for anemia other than CKD.

  9. Red blood cell transfusion within 6 weeks prior to the first screening visit.

  10. More than one dose of IV iron was received within 12 weeks prior to recruiting.

  11. History of uncontrolled chronic, severe, fulminant, autoimmune, or end-stage liver disease with Aspartate aminotransferase( AST), alanine aminotransferase (ALT) > 3 × upper limit normal (ULN), or total bilirubin > 1.5 × ULN. 12. Any clinically significant inflammatory disorders other than CKD, as any evidence of an active underlying infection, rheumatoid arthritis, systemic lupus, or cancer.

  13. Known and untreated retinal vein occlusion or proliferative diabetic retinopathy, macular degeneration, diabetic macular edema.

  14. Prior organ transplant or a scheduled organ transplantation date. 15. Planning for pregnancy, pregnant, or breastfeeding female patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oral low doses of Roxadustat three times weekly plus iron supplement,	Drug: Roxadustat; hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs); Other Names: hypoxia-inducible factor- prolyl hydroxylase enzyme inhibitor
Active Comparator: Erythropoiesis-stimulating agents (ESAs)	Drug: Roxadustat; hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs); Other Names: hypoxia-inducible factor- prolyl hydroxylase enzyme inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in hemoglobin level from baseline	HB g/dl	3 months
Iron metabolism parameters change from the baseline	serum iron µg/ml , ferritin µg/l, Total Iron Binding Capacity µg/ml (TIBC) levels, and transferrin saturation (TSAT)%	3 months
Safety profile	adverse events will be reported using a pre-prepared checklist	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to achieve and maintain HB target	desired level (HB) 10-12 g/dL	3 months
The need for rescue therapy	For the Roxadustat-treated participants (intervention arm) rescue therapy is defined as, red blood cell (RBC) transfusion or erythropoiesis-stimulating agent (ESA).; For erythropoiesis-stimulating agents (ESA) (control arm) rescue therapy is defined as RBC transfusion	3 months
The minimum effective dose in combination with iron is needed to achieve the HB target.		3 months
Change in hepcidin level in the intervention group		3 months
Change in the Quality of Life (QoL) of the patients after the completion of the study period	Arabic-translated reliable and valid version of the Kidney Disease Quality of Life questionnaire (KDQOL-36) for patients with CKD	3 months

Collaborators and Investigators

• Sponsor: Alexandria University

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2023
• Primary Completion (Actual): August 30, 2024
• Study Completion (Actual): January 30, 2025

Study Registration Dates

• First Submitted: October 15, 2023
• First Submitted That Met QC Criteria: October 29, 2023
• First Posted (Actual): November 3, 2023

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Dialysis-dependent CKD patients ,anemia ,hypoxia-inducible factor-; Roxadustatse
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Hematologic Diseases; Renal Insufficiency; Signs and Symptoms, Respiratory; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Anemia; Hypoxia; Molecular Mechanisms of Pharmacological Action; roxadustat
• Other Study ID Numbers: 0201793

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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