Ferric Citrate for the Treatment of Hyperphosphatemia in Patients With Chronic Kidney Disease Undergoing Hemodialysis

Phase 3

Completed

• Conditions: ESRD; Hyperphosphatemia; End Stage Renal Disease
• Interventions: Drug: Ferric citrate tablet; Drug: Sevelamer carbonate tablet

• Registration Number: NCT04456803
• Lead Sponsor: Sinomune Pharmaceutical Co., Ltd

Brief Summary

To evaluate the efficacy and safety of ferric citrate tablet in the control of serum phosphorus levels in patients with chronic kidney disease undergoing hemodialysis.

Detailed Description

This is a multicenter, randomized, open-label, parallel, phase III study. This study is consisting of a Screening/Washout period (14 days) and a Treatment/Observation period (12 weeks). The subjects with regular hemodialysis should stop using the phosphorus binder before the Washout period. During the Treatment period, the subjects will be randomly assigned to the ferric citrate tablets group (study group) or sevelamer carbonate tablet group (control group) in the ratio of 1:1.

Study Timeline

• Study Start: 2019-05-24
• Study First Submitted: 2020-06-30
• Study First Submitted QC: 2020-06-30
• Study First Posted: 2020-07-07
• Primary Completion: 2022-09-13
• Study Completion: 2022-09-13
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-16
• Last Update Posted: 2024-04-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 239

Inclusion Criteria

1. Between the age of 18 and 75 years (including the boundary value) and no gender limitation;
2. Patients who maintain the hemodialysis schedule (including hemofiltration (HF) hemodialysis (HDF) hemoperfusion (HP)) as not less than 3 times a week in the 3 months before random enrollment.
3. Patients with a serum phosphorus level between 1.97 to 3.23 mmol/L (excluding the boundary value) after washout.
4. Kt/Vurea ≥1.2 or URR ≥65%.
5. Before the screening period, CKD-MBD related drug treatment is stable for more than one month, including the use of vitamin D (active vitamin D, vitamin D analogues, etc.) or calcimimetics (cinacalcet, etc.) and the dose remains unchanged.
6. The expected survival is greater than 6 months.
7. Willing to give written informed consent.

Exclusion Criteria

1. Patients with a serum ferritin level ≥800 ng/mL or TSAT ≥50%.
2. Patients with hemochromatosis or patients receiving treatment for iron overload, or patients with paroxysmal sleep hemoglobinuria.
3. Patients who received blood transfusions within 3 months prior to Screening, or patients with hemoglobin ≤60 g/L.
4. Patients with intact-PTH >1000 pg/mL
5. Patients complicated with any of the following gastrointestinal diseases: acute peptic ulcer, chronic ulcerative colitis, localized enteritis, intestinal obstruction, habitual constipation (number of stools once per week), and chronic diarrhea (number of stools four times per day), or patients with a history of gastrectomy or enterectomy or patients who had undergone gastrointestinal surgery within 3 months prior to Screening, or patients with dysphagia.
6. Patients with impaired liver function (hepatic dysfunction or serum total bilirubin, aspartate aminotransferase or alanine aminotransferase ≥ 2 times the upper limit of normal) or patients with cirrhosis.
7. Patients with a history of parathyroidectomy (PTx) or percutaneous anhydrous ethanol injection (PEIT) within 6 months.
8. Patients with uncontrolled diabetes or uncontrolled high blood pressure or current active infectious diseases such as active viral hepatitis.
9. Patients with a history of severe allergies may be allergic to research drugs.
10. Patients with cerebrovascular disease (cerebral infarction, cerebral hemorrhage, etc.) or cardiovascular disease (congestive heart failure of Class III or severer in NYHA classification) requiring hospitalization within 6 months prior to Screening, or patients who use antiarrhythmic drugs to control arrhythmias or who use antiepileptic drugs to control seizures.
11. Patients who plan to receive a kidney transplant during the study period.
12. Patients with a history of drug and alcohol abuse
13. Patients with active or advanced malignancy.
14. Women who are pregnant or lactating
15. Patients complicated with active bleeding or requiring anticoagulation therapy with citrate in hemodialysis
16. Patients who had participated in other clinical studies within 1 month prior to Screening.
17. Patients who are not suitable for participating in the trial according to the investigator's judgment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ferric citrate tablet	Ferric citrate tablet	Ferric citrate arm will receive ferric citrate tablets three times a day with each meal.
Sevelamer carbonate tablet	Sevelamer carbonate tablet	Sevelamer carbonate arm will receive sevelamer carbonate tablets three times a day with each meal.

Primary Outcome Measures

Name	Time	Method
The change in serum phosphorus levels	12 Weeks	The change in serum phosphorus levels at the end of treatment as compared to baseline (before the first dose).

Secondary Outcome Measures

Name	Time	Method
The change in the level of intact-PTH levels.	week 4, 8 and 12	The change in the level of intact-PTH levels at week 4, 8 and 12 of treatment as compared to baseline.
The proportion of subjects whose serum phosphorus levels reached the target	week 4, 6, 8 and 12	The proportion of subjects whose serum phosphorus levels reached the target range at week 4, 6, 8 and 12 of treatment (the standard was defined as blood phosphorus ≤1.78mmol /L, and ≥1.13mmol /L).
Changes in serum phosphorus levels	week 2, 4, 6, 8	Changes in serum phosphorus levels from baseline
Area under the curve of serum phosphorus level	week 0, 2, 4, 6, 8, 12	Area under the curve of serum phosphorus level to visit time (AUC 0-12 weeks)
The change in serum calcium (corrected) levels.	week 4, 8 and 12	The change in serum calcium (corrected) levels at week 4, 8 and 12 of treatment as compared to baseline.

Trial Locations

Locations (20)

The second hospital of Dalian medical university; 🇨🇳 Dalian, China

The second people's hospital of Huaian; 🇨🇳 Huai'an, China

Zhuzhou Central Hospital; 🇨🇳 Zhuzhou, China

The first affiliated hospital of Baotou medical college; 🇨🇳 Baotou, China

Beijing Tongren Hospital; 🇨🇳 Beijing, China

Peking Union Medical College Hospital; 🇨🇳 Beijing, China

The Second Xiangya Hospital of Central South University; 🇨🇳 Changsha, China

Xiangya Hospital Central South University; 🇨🇳 Changsha, China

The affiliated hospital of Inner Mongolia Medical University; 🇨🇳 Hohhot, China

Shandong province Qianfoshan hospital; 🇨🇳 Jinan, China

Zhongnan Hospital Southeast University; 🇨🇳 Nanjing, China

The people's hospital of Guangxi Zhuang Autonomous Region; 🇨🇳 Nanning, China

Jinan central hospital; 🇨🇳 Jinan, China

The third hospital of Hebei medical university; 🇨🇳 Shijiazhuang, China

First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, China

Shenzhen people's hospital; 🇨🇳 Shenzhen, China

General Hospital of Tianjin Medical University; 🇨🇳 Tianjin, China

Henan provincal people's hospital; 🇨🇳 Zhengzhou, China

Zhengzhou People's Hospital; 🇨🇳 Zhengzhou, China

The First Affiliated Hospital of Xinjiang Medical University; 🇨🇳 Ürümqi, China