Clinical trial NCT06115421: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Anemia in Dialysis-dependent CKD Patients
Keywords: Dialysis-dependent CKD patients ,anemia ,hypoxia-inducible factor-
Roxadustatse
Lead sponsor: Alexandria University
Sponsor class: OTHER
First posted: 2023-11-03
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: two-arm open-label non randomized active control study
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Changes in hemoglobin level from baseline
timeFrame: 3 months
measure: Iron metabolism parameters change from the baseline
timeFrame: 3 months
measure: Safety profile
timeFrame: 3 months
Secondary outcomes:
measure: Time to achieve and maintain HB target
timeFrame: 3 months
measure: The need for rescue therapy
timeFrame: 3 months
measure: The minimum effective dose in combination with iron is needed to achieve the HB target.
timeFrame: 3 months
measure: Change in hepcidin level in the intervention group
timeFrame: 3 months
measure: Change in the Quality of Life (QoL) of the patients after the completion of the study period
timeFrame: 3 months
Other outcomes:
Locations:
city: Alexandria
country: Egypt
facility: Alexandria University
Study officials:
References: