دورية أكاديمية
PROPEL: a randomized trial of mericitabine plus peginterferon alpha-2a/ribavirin therapy in treatment-naïve HCV genotype 1/4 patients.
| العنوان: | PROPEL: a randomized trial of mericitabine plus peginterferon alpha-2a/ribavirin therapy in treatment-naïve HCV genotype 1/4 patients. |
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| المؤلفون: | Wedemeyer H; Medizinische Hochschule, Hannover, Germany., Jensen D, Herring R Jr, Ferenci P, Ma MM, Zeuzem S, Rodriguez-Torres M, Bzowej N, Pockros P, Vierling J, Ipe D, Munson ML, Chen YC, Najera I, Thommes J |
| مؤلفون مشاركون: | PROPEL Investigators |
| المصدر: | Hepatology (Baltimore, Md.) [Hepatology] 2013 Aug; Vol. 58 (2), pp. 524-37. Date of Electronic Publication: 2013 Jun 26. |
| نوع المنشور: | Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wolters Kluwer Health, Inc Country of Publication: United States NLM ID: 8302946 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-3350 (Electronic) Linking ISSN: 02709139 NLM ISO Abbreviation: Hepatology Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : [Philadelphia] : Wolters Kluwer Health, Inc. Original Publication: Baltimore, MD : Williams & Wilkins, [c1981]- |
| مواضيع طبية MeSH: | Genotype*, Deoxycytidine/*analogs & derivatives , Hepacivirus/*genetics , Hepatitis C, Chronic/*drug therapy , Interferon-alpha/*therapeutic use , Polyethylene Glycols/*therapeutic use , Ribavirin/*therapeutic use, Adolescent ; Adult ; Aged ; Deoxycytidine/pharmacology ; Deoxycytidine/therapeutic use ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Interferon-alpha/pharmacology ; Interferons ; Interleukins/genetics ; Male ; Middle Aged ; Polyethylene Glycols/pharmacology ; RNA, Viral/drug effects ; RNA, Viral/genetics ; Recombinant Proteins/pharmacology ; Recombinant Proteins/therapeutic use ; Ribavirin/pharmacology ; Treatment Outcome ; Young Adult |
| مستخلص: | Unlabelled: Mericitabine is a nucleoside analog polymerase inhibitor of hepatitis C virus (HCV). Treatment-naïve HCV genotype 1 or 4 patients were randomized to double-blind treatment with oral mericitabine at a dosage of 500 mg twice-daily (BID) for 12 weeks (A), 1,000 mg BID for 8 (B) or 12 weeks (C and D), or placebo BID for 12 weeks (E). All patients received pegylated interferon alpha-2a (Peg-IFNα-2a; 40 kD)/ribavirin (RBV) at standard doses for 24 or 48 weeks during and after mericitabine/placebo therapy. Patients in arms A-C who maintained a virologic response (VR) (HCV RNA <15 IU/mL) from weeks 4 to 22 stopped all treatment at week 24; all other patients (arms A-E) continued Peg-IFNα-2a/RBV to complete 48 weeks. The primary outcome was sustained VR (SVR) (HCV RNA <15 IU/mL after 24 weeks of untreated follow-up; SVR-24). VR rates were higher in arms A-D than in arm E at weeks 4 and 12 overall, in patients with and without cirrhosis and in patients with CC and non-CC IL28B genotypes. However, the overall SVR-24 rate in arms D (50.6%) and E (placebo, 51.2%) was similar and those in the response-guided therapy arms A, B, and C were lower (48.8%, 42.0%, and 32.9%, respectively). No viral breakthrough or mericitabine-resistance mutations (S282T) were observed during mericitabine therapy. Conclusion: Treatment with mericitabine plus Peg-IFNα-2a/RBV for 8 or 12 weeks provided potent suppression of HCV RNA, was well tolerated, and did not select resistant variants, but did not increase SVR rates, compared to placebo. IFN-free and IFN-containing trials of mericitabine of longer treatment duration are ongoing. (Copyright © 2013 American Association for the Study of Liver Diseases.) |
| التعليقات: | Comment in: Hepatology. 2013 Aug;58(2):488-90. (PMID: 24058936) |
| فهرسة مساهمة: | Investigator: K Agarwal; P Andreone; Y Benhamou; T Berg; J Bloomer; J- Bronowicki; MR Brunetto; S Bruno; JL Calleja; MA Iglesias; W Cheng; A Ciancio; V Clark; D Crawford; V de Lédinghen; P Desmond; M Diago; N Dikopoulos; B Freilich; E Godofsky; T Hassanein; C Hézode; I Jacobson; DM Klass; A Kuo; SS Lee; B Leggett; GA Macdonald; G Mac-Quillan; P Marotta; R Vila; S Pol; A Ramji; JW Rasenack; V Ratziu; S Roberts; M Romero-Gómez; W Rosenberg; L Rossaro; FJ Salmeron; JM Sánchez-Tapias; AJ Sanyal; A Scuteri; T Sepe; A Sheikh; M Sherman; GL Simon; J Slim; JP Smith; R Solà; SI Strasser; J Strohecker; M Sulkowski; A Tran; B Willems; E Yoshida; R Zachoval; J- Zarski |
| المشرفين على المادة: | 0 (2'-fluoro-2'-methyl-3',5'-diisobutyryldeoxycytidine) 0 (interferon-lambda, human) 0 (Interferon-alpha) 0 (Interleukins) 0 (RNA, Viral) 0 (Recombinant Proteins) 0W860991D6 (Deoxycytidine) 3WJQ0SDW1A (Polyethylene Glycols) 49717AWG6K (Ribavirin) 9008-11-1 (Interferons) Q46947FE7K (peginterferon alfa-2a) |
| تواريخ الأحداث: | Date Created: 20130126 Date Completed: 20140116 Latest Revision: 20231213 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1002/hep.26274 |
| PMID: | 23348636 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1527-3350 |
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| DOI: | 10.1002/hep.26274 |