現在位置 : 腎病 > 腎病藥物 > 活性炭 克裏美淨(Kremezin)效果不明顯 - 研究報告
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Charcoal Therapy Fails to Curb CKD Progress
2012-11-4 by Kristina Fiore Staff Writer, MedPage Today SAN DIEGO -- A form of charcoal pill doesn't appear to slow the progression of chronic kidney disease (CKD), researchers said here. In a pooled analysis of two randomized controlled trials, similar proportions of patients taking either placebo or the charcoal pill AST-120 (marketed as Kremezin in Japan) reached a primary composite endpoint of time to dialysis, kidney transplant, or doubling of serum creatinine (36% and 35%, respectively), reported Gerald Schulman, MD, of Vanderbilt University in Nashville, and colleagues during a late-breaking poster session at Kidney Week. "Unfortunately, this study did not show for the whole cohort...a difference between placebo and the active drug as opposed to in Japan, where many studies suggested that it did slow progression," Schulman told MedPage Today. AST-120 is a spherical charcoal absorbent that was approved in Japan in 1991 for prolonging time to dialysis and improving uremic symptoms in patients with CKD. Charcoal has other common medical uses, typically administered during poisonings for its ability to concentrate unwanted uremic compounds. One of those compounds is indole, Schulman explained, which gets converted to indoxyl sulfate and ultimately gets into the kidney, where it leads to fibrosis. In order to assess whether adding AST-120 to standard therapy in patients with moderate-to-severe CKD slowed disease progression, Schulman and colleagues led two trials in the Evaluating Prevention of Progression in CKD (EPPIC) series, conducted at 237 sites in the Americas and Europe. They pooled results of those two phase III trials, totaling 2,035 patients who were randomized to either 9 g/day of AST-120 -- via 10 300-mg capsules taken three times daily -- or to placebo, in addition to standard care with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB). The composite primary endpoint was time to initiation of dialysis, kidney transplant, or doubling of serum creatinine, and the secondary endpoint was a composite of the primary endpoint plus mortality. In addition to a similar proportion of patients reached the primary composite endpoint in both groups, similar proportions of patients also reached the secondary composite endpoint, they reported (41.7% versus 41.8%). The safety profile of AST-120 was similar to that of placebo, they found. Schulman noted that his team conducted a post-hoc subgroup analysis and found several factors that were predictive of better results with the drug. "For patients who were deemed to be compliant with the drug, had proteinuria, and hematuria, you can see there is a difference," he told MedPage Today. "But the study was [focused] on the entire cohort, so it's intention-to-treat. We cannot prove efficacy." Schulman said it's still not clear why the drug works in the Japanese population for this indication, but not in their Americas and Europe study population. "I hope further studies will be done," he said, noting that developing treatments to counteract kidney fibrosis in general is a "very hot area of research now." The studies were sponsored by Mitsubishi Tanabe Pharma and Kureha. The researchers reported no conflicts of interest. Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner Primary Source Kidney Week Source Reference: Schulman G, et al "EPPIC (evaluating prevention of progression in CKD -- results from two phase III, randomized, placebo-controlled, double-blind trials of AST-120 in adults with CKD" ASN 2012. |
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Kremezin Side Effects and Adverse Effects reported to US Food and Drug Administration (FDA)
Bleeding Time Prolonged, Thrombocytopenia (8422664-8) on May 29, 2012 Male from JAPAN , weighting 72.75 lb, was diagnosed with •renal failure chronic •hyperuricaemia •hypertension and was treated with Kremezin. Directly after, patient experienced the unwanted or unexpected Kremezin side effects: bleeding time prolonged, thrombocytopenia. Kremezin dosage: N/A. Associated medications used: •Allopurinol •Lasix (40-80mg) •Uralyt •Mircera •Famotidine Patient was hospitalized. Thirst (8349082-5) Patient was taking Kremezin (charcoal, Activated). Patient felt the following Kremezin side effects: thirst on Apr 21, 2012 from JAPAN Additional patient health information: Male , 87 years of age, weighting 167.6 lb, . Kremezin (charcoal, Activated) dosage: N/A. Multiple prescriptions taken: •Lansoprazole •Samsca (15 Mg Milligram(s), Qam, Oral) •Diart (azosemide) Tablet (60 Mg Milligram(s), Daily Dose, Oral) •Coughnol (ambroxol Hydrochloride) •Warfarin Sodium •Glucose (ascorbic Acid, Glucose) •Lasix (40 Mg Milligram(s), Daily Dose, Oral) •Calblock (azelnidipine) Interstitial Lung Disease (8345422-1) Adverse event was reported on Apr 19, 2012 by a Male taking Kremezin (charcoal, Activated) (Dosage: N/A) . Location: JAPAN , 79 years of age, After Kremezin was administered, patient encountered several Kremezin side effects: interstitial lung disease. Multiple concurrent drugs taken: •Famotidine •Warfarin Sodium •Lanirapid (metildigoxin) •Pletal (100 Mg Milligram(s), Bid, Oral) •Amoban (zopiclone) •Ferromia (sodium Ferrous Citrate) •Furosemide Patient was hospitalized. Angioedema, Renal Failure, Blood Pressure Increased, Nephrogenic Anaemia (8270425-5) on Mar 28, 2012 Female from JAPAN , weighting 127.9 lb, was treated with Kremezin. Directly after, patient experienced the unwanted or unexpected Kremezin side effects: angioedema, renal failure, blood pressure increased, nephrogenic anaemia. Kremezin dosage: 6 G. Associated medications used: •Irbesartan (300 Mg) •Kayexalate (15 G) •Acetaminophen (600 Mg) •Aliskiren (150 Mg, Daily) •Amlodipine (10 Mg,) •Irbesartan (200 Mg) •Aliskiren (300 Mg, Daily) •Depas (1.5 Mg) Face Oedema, Thrombocytopenia, Alanine Aminotransferase Increased, Blood Urea Increased, Oedema Peripheral, Hypothyroidism, Aspartate Aminotransferase Increased, Malaise, Palmar-plantar Erythrodysaesthesia Syndrome (7930125-5) on Nov 18, 2011 Male from JAPAN , 70 years of age, was treated with Kremezin. Patient felt the following Kremezin side effects: face oedema, thrombocytopenia, alanine aminotransferase increased, blood urea increased, oedema peripheral, hypothyroidism, aspartate aminotransferase increased, malaise, palmar-plantar erythrodysaesthesia syndrome. Kremezin dosage: Unk. Multiple prescriptions taken: •Magnesium Oxide (Unk) •Losartan Potassium (Unk) •Rabeprazole Sodium (Unk) •Persantin (Unk) •Amlodipine (Unk) •Sunitinib Malate (50 Mg, 1x/day, 28-day Administration And 14-day Cessation) •Sunitinib Malate (37.5 Mg/day) •Gaslon (Unk) Patient was hospitalized. Malaise, Face Oedema, Aspartate Aminotransferase Increased, Blood Urea Increased, Thrombocytopenia, Palmar-plantar Erythrodysaesthesia Syndrome, Alanine Aminotransferase Increased, Oedema Peripheral, Blood Creatinine Increased (7861371-7) Patient was taking Kremezin. After Kremezin was administered, patient encountered several Kremezin side effects: malaise, face oedema, aspartate aminotransferase increased, blood urea increased, thrombocytopenia, palmar-plantar erythrodysaesthesia syndrome, alanine aminotransferase increased, oedema peripheral, blood creatinine increased on Oct 20, 2011 from JAPAN Additional patient health information: Male , 70 years of age, . Kremezin dosage: Unk. Multiple concurrent drugs taken: •Amaryl (Unk) •Amlodipine (Unk) •Rabeprazole Sodium (Unk) •Gaslon (Unk) •Sunitinib Malate (50 Mg, 1x/day, 28-day Administration And 14-day Cessation) •Sunitinib Malate (37.5 Mg/day) •Magnesium Oxide (Unk) •Persantin (Unk) Patient was hospitalized. Renal Failure Chronic (7555681-0) Adverse event was reported on Jun 01, 2011 by a Male taking Kremezin (Dosage: N/A) . Location: SWITZERLAND , weighting 172.0 lb, Directly after, patient experienced the unwanted or unexpected Kremezin side effects: renal failure chronic. Patient was hospitalized. Diabetic Ketoacidosis, Cerebral Infarction, Cerebral Haemorrhage, Diabetic Neuropathy, Cardiac Failure, Vomiting (7437495-5) on Apr 20, 2011 Female from JAPAN , 63 years of age, weighting 97.00 lb, was treated with Kremezin. Patient felt the following Kremezin side effects: diabetic ketoacidosis, cerebral infarction, cerebral haemorrhage, diabetic neuropathy, cardiac failure, vomiting. Kremezin dosage: N/A. Multiple prescriptions taken: •Apidra (Continuous Subcutaneous Insulin Infusion (csii)) •Apidra (Continuous Subcutaneous Insulin Infusion (csii)) •Apidra (Continuous Subcutaneous Insulin Infusion (csii)) Patient was hospitalized. Peritonitis, Rectal Perforation (7437335-4) on Apr 21, 2011 Female from JAPAN , 57 years of age, was treated with Kremezin. After Kremezin was administered, patient encountered several Kremezin side effects: peritonitis, rectal perforation. Kremezin dosage: N/A. Multiple concurrent drugs taken: •Diovan •Calblock •Loxonin •Alfarol •Cytotec •Fosrenol (750 Mg, Unk) •Zyloric •Thyradin |
