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| Name | Class |
|---|---|
| Conmed Pharmaceutical & Bio-Medical Corporation | INDUSTRY |
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The primary goal of this clinical trial is to evaluate the efficacy of AST-120 (Kremezin®) in combination with standard care in reducing the levels of protein-bound uremic toxins (PBUTs), specifically indoxyl sulfate (IS) and p-cresyl sulfate (p-CS), in patients with acute kidney disease (AKD). The trial aims to assess whether AST-120 can prevent further renal deterioration and slow the progression from AKD to chronic kidney disease (CKD) by mitigating the accumulation of PBUTs. Additionally, the study will investigate the potential of AST-120 to reduce the risk of CKD-associated complications, including cardiovascular disease, by reducing PBUT levels in AKD patients.
Study Procedures:
The study will include two groups:
2. Interventions, Procedures, and Tests for Each Group
Subjects will undergo the following interventions, procedures, and tests according to the schedule:
Baseline (Day 0):
- Demographic data collection.
Treatment Period (Day 1-14):
Day 14:
Blood tests for IS, p-CS, serum creatinine, eGFR, and UACR.
Follow-up (Day 90 and Day 180):
Assess eGFR, serum creatinine, UACR.
Monitor for major adverse kidney events (MAKE) and major adverse cardiovascular events (MACE).
3. Trial Procedure Timeline
The trial procedure follows this timeline:
4. Specimen Collection and Processing
Specimen: Blood samples will be collected on Day 0 (baseline), Day 14 (end of treatment), Day 90, and Day 180 (follow-up).
Transport and Storage: Specimens will be transported to the laboratory within the hospital for immediate processing. They will be stored in a temperature-controlled facility if needed.
Processing: Blood samples will undergo centrifugation for serum separation. Serum will be used for measuring IS, p-CS, serum creatinine, and other biomarkers.
Analysis: The following tests will be performed:
IS and p-CS levels.
Serum creatinine and eGFR.
UACR.
5. Clinical Data Collection and Questionnaires
Clinical data collected will include:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | No Intervention | Control (Standard Care Only) Intervention: Standard post-AKD care No AST-120 | |
| Experimental (AST-120 + Standard Care) | Experimental | Intervention: AST-120 (Kremezin®) Dosage: 6 g/day (2 g TID, oral) Duration: 14 days Background treatment: Standard post-AKD care |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AST-120 (Kremezin®) | Drug | AST-120 (Kremezin®) Dosage: 6 g/day (2 g TID, oral) Duration: 14 days Background treatment: Standard post-AKD care |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in serum indoxyl sulfate (IS) concentration | Change in serum indoxyl sulfate (IS) concentration Time Frame: Baseline to Day 180 Description: Evaluate reduction in IS levels after AST-120 treatment compared to control. | Day 0, Day 14, Day 90, Day 180 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in serum p-cresyl sulfate (p-CS) concentration | Change in serum p-cresyl sulfate (p-CS) concentration Time Frame: Baseline to Day 180 Assess difference in p-CS levels between groups. | Day 0, Day 14, Day 90, Day 180 |
| Change in estimated glomerular filtration rate (eGFR) |
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Inclusion/Exclusion Criteria: Inclusion criteria
Exclusion criteria
1. Patients presenting any of the following conditions, considered as excessively vulnerable populations or other conditions:
Patients unsuitable for AST-120 treatment, including:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Chih-Hsiang Chang | Contact | (03) 3196200 | 7761 | franwisandsun@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chang Gung Memorial Hospital, Taoyuan, Taiwan | Recruiting | Taoyuan | 333 | Taiwan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35622583 | Background | Caillard P, Bennis Y, Six I, Bodeau S, Kamel S, Choukroun G, Maizel J, Titeca-Beauport D. The Role of Gut-Derived, Protein-Bound Uremic Toxins in the Cardiovascular Complications of Acute Kidney Injury. Toxins (Basel). 2022 May 11;14(5):336. doi: 10.3390/toxins14050336. | |
| 26395517 | Background | Yamamoto S, Kazama JJ, Omori K, Matsuo K, Takahashi Y, Kawamura K, Matsuto T, Watanabe H, Maruyama T, Narita I. Continuous Reduction of Protein-Bound Uraemic Toxins with Improved Oxidative Stress by Using the Oral Charcoal Adsorbent AST-120 in Haemodialysis Patients. Sci Rep. 2015 Sep 23;5:14381. doi: 10.1038/srep14381. |
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| ID | Term |
|---|---|
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| C040896 | AST 120 |
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Experimental Group (AST-120 Treatment Group):
Control Group (Standard Post-AKD Care Only):
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Change in estimated glomerular filtration rate (eGFR) Time Frame: Baseline to Day 180 Description: Evaluate reduction in eGFR after AST-120 treatment compared to control. |
| Day 0, Day 14, Day 90, Day 180 |
| Change in urine albumin/creatinine ratio (UACR) | Change in urine albumin/creatinine ratio (UACR) Time Frame: Baseline to Day 180 Description: Evaluate reduction inUACR after AST-120 treatment compared to control. | Day 0, Day 14, Day 90, Day 180 |
| Change in urine total protein/creatinine ratio (UPCR) | Change in urine total protein/creatinine ratio (UPCR) Time Frame: Baseline to Day 180 Description: Evaluate reduction in UPCR after AST-120 treatment compared to control. | Day 0, Day 14, Day 90, Day 180 |
| 33311993 | Background | Nagata D, Yoshizawa H. Pharmacological Actions of Indoxyl Sulfate and AST-120 That Should Be Recognized for the Strategic Treatment of Patients with Chronic Kidney Disease. Int J Nephrol Renovasc Dis. 2020 Dec 4;13:359-365. doi: 10.2147/IJNRD.S287237. eCollection 2020. |
| 33658826 | Background | Shen WC, Chou YH, Shi LS, Chen ZW, Tu HJ, Lin XY, Wang GJ. AST-120 Improves Cardiac Dysfunction in Acute Kidney Injury Mice via Suppression of Apoptosis and Proinflammatory NF-kappaB/ICAM-1 Signaling. J Inflamm Res. 2021 Feb 24;14:505-518. doi: 10.2147/JIR.S283378. eCollection 2021. |
| 33668632 | Background | Lim YJ, Sidor NA, Tonial NC, Che A, Urquhart BL. Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets. Toxins (Basel). 2021 Feb 13;13(2):142. doi: 10.3390/toxins13020142. |
| 32384617 | Background | Espi M, Koppe L, Fouque D, Thaunat O. Chronic Kidney Disease-Associated Immune Dysfunctions: Impact of Protein-Bound Uremic Retention Solutes on Immune Cells. Toxins (Basel). 2020 May 6;12(5):300. doi: 10.3390/toxins12050300. |
| 25349205 | Background | Schulman G, Berl T, Beck GJ, Remuzzi G, Ritz E, Arita K, Kato A, Shimizu M. Randomized Placebo-Controlled EPPIC Trials of AST-120 in CKD. J Am Soc Nephrol. 2015 Jul;26(7):1732-46. doi: 10.1681/ASN.2014010042. Epub 2014 Oct 27. |
| 22237753 | Background | Sun CY, Chang SC, Wu MS. Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int. 2012 Apr;81(7):640-50. doi: 10.1038/ki.2011.445. Epub 2012 Jan 11. |
| 35050985 | Background | Chen JH, Chiang CK. Uremic Toxins and Protein-Bound Therapeutics in AKI and CKD: Up-to-Date Evidence. Toxins (Basel). 2021 Dec 23;14(1):8. doi: 10.3390/toxins14010008. |
| 22610984 | Background | Sun CY, Hsu HH, Wu MS. p-Cresol sulfate and indoxyl sulfate induce similar cellular inflammatory gene expressions in cultured proximal renal tubular cells. Nephrol Dial Transplant. 2013 Jan;28(1):70-8. doi: 10.1093/ndt/gfs133. Epub 2012 May 18. |
| 19696217 | Background | Barreto FC, Barreto DV, Liabeuf S, Meert N, Glorieux G, Temmar M, Choukroun G, Vanholder R, Massy ZA; European Uremic Toxin Work Group (EUTox). Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clin J Am Soc Nephrol. 2009 Oct;4(10):1551-8. doi: 10.2215/CJN.03980609. Epub 2009 Aug 20. |
| 24501542 | Background | Schulman G, Vanholder R, Niwa T. AST-120 for the management of progression of chronic kidney disease. Int J Nephrol Renovasc Dis. 2014 Jan 30;7:49-56. doi: 10.2147/IJNRD.S41339. eCollection 2014. |
| 34167119 | Background | Levey AS. Defining AKD: The Spectrum of AKI, AKD, and CKD. Nephron. 2022;146(3):302-305. doi: 10.1159/000516647. Epub 2021 Jun 24. |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |