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10.3310/eme08170 http://scihub22266oqcxt.onion/10.3310/eme08170 34723451!ä!34723451 Deprecated: Implicit conversion from float 265.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 299.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 299.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 299.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 299.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 299.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 299.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 332.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 332.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Variable+short+duration+treatment+versus+standard+treatment,+with+and+without++adjunctive+ribavirin,+for+chronic+hepatitis+C:+the+STOP-HCV-1+non-inferiority,++factorial+RCT-/-Efficacy+and+Mechanism+Evaluation 2021 ; ä (ä): ä Nephropedia Template TP {{tp|p=34723451|t=2021. Variable short duration treatment versus standard treatment, with and without adjunctive ribavirin, for chronic hepatitis C: the STOP-HCV-1 non-inferiority, factorial RCT|pdf=|usr=}}{{34723451}} gab.com Text Variable short duration treatment versus standard treatment, with and without adjunctive ribavirin, for chronic hepatitis C: the STOP-HCV-1 non-inferiority, factorial RCT JO: Variable short duration treatment versus standard treatment, with and without adjunctive ribavirin, for chronic hepatitis C: the STOP-HCV-1 non-inferiority, factorial RCT-/-Efficacy and Mechanism Evaluation http://www.kidney.de/pget.php?&tw=1&pmid=34723451 #FOAvip BACKGROUND: High cure rates with licensed durations of therapy for chronic hepatitis C virus suggest that many patients are overtreated. New strategies in individuals who find it challenging to adhere to standard treatment courses could significantly contribute to the elimination agenda. OBJECTIVES: To compare cure rates using variable ultrashort first-line treatment stratified by baseline viral load followed by retreatment, with a fixed 8-week first-line treatment with retreatment with or without adjunctive ribavirin. DESIGN: An open-label, multicentre, factorial randomised controlled trial. RANDOMISATION: Randomisation was computer generated, with patients allocated in a 1 : 1 ratio using a factorial design to each of biomarker-stratified variable ultrashort strategy or fixed duration and adjunctive ribavirin (or not), using a minimisation algorithm with a probabilistic element. SETTING: NHS. PARTICIPANTS: A total of 202 adults (aged >/= 18 years) infected with chronic hepatitis C virus genotype 1a/1b or 4 for >/= 6 months, with a detectable plasma hepatitis C viral load and no significant fibrosis [FibroScan((R)) (Echosens, Paris, France) score F0-F1 or biopsy-proven minimal fibrosis], a hepatitis C virus viral load < 10,000,000 IU/ml, no previous exposure to direct-acting antiviral therapy for this infection and not pregnant. Patients co-infected with human immunodeficiency virus were eligible if human immunodeficiency virus viral load had been < 50 copies/ml for > 24 weeks on anti-human immunodeficiency virus drugs. INTERVENTIONS: Fixed-duration 8-week first-line therapy compared with variable ultrashort first-line therapy, initially for 4-6 weeks (continuous scale) stratified by screening viral load (variable ultrashort strategy 1, mean 32 days of treatment) and then, subsequently, for 4-7 weeks (variable ultrashort strategy 2 mean 39 days of duration), predominantly with ombitasvir, paritaprevir, ritonavir (Viekirax((R)); AbbVie, Chicago, IL, USA), and dasabuvir (Exviera((R)); AbbVie, Chicago, IL, USA) or ritonavir. All patients in whom first-line treatment was unsuccessful were immediately retreated with 12 weeks' sofosbuvir, ledipasvir (Harvoni((R)), Gilead Sciences, Inc., Foster City, CA, USA) and ribavirin. MAIN OUTCOME MEASURE: The primary outcome was overall sustained virological response (persistently undetectable) 12 weeks after the end of therapy (SVR12). RESULTS: A total of 202 patients were analysed. All patients in whom the primary outcome was evaluable achieved SVR12 overall [100% (197/197), 95% confidence interval 86% to 100%], demonstrating non-inferiority between fixed- and variable-duration strategies (difference 0%, 95% confidence interval -3.8% to 3.7%, prespecified non-inferiority margin 4%). A SVR12 following first-line treatment was achieved in 91% (92/101; 95% confidence interval 86% to 97%) of participants randomised to the fixed-duration strategy and by 48% (47/98; 95% confidence interval 39% to 57%) allocated to the variable-duration strategy. However, the proportion achieving SVR12 was significantly higher among those allocated to variable ultrashort strategy 2 [72% (23/32), 95% confidence interval 56% to 87%] than among those allocated to variable ultrashort strategy 1 [36% (24/66), 95% confidence interval 25% to 48%]. Overall, a SVR12 following first-line treatment was achieved by 72% (70/101) (95% confidence interval 65% to 78%) of patients treated with ribavirin and by 68% (69/98) (95% confidence interval 61% to 76%) of those not treated with ribavirin. A SVR12 with variable ultrashort strategies 1 and 2 was 52% (25/48) (95% confidence interval 38% to 65%) with ribavirin, compared with 44% (22/50) (95% confidence interval 31% to 56) without. However, at treatment failure, the emergence of viral resistance was lower with ribavirin [12% (3/26), 95% confidence interval 2% to 30%] than without [38% (11/29), 95% confidence interval 21% to 58%; p = 0.01]. All 10 individuals who became undetectable at day 3 of treatment achieved first-line SVR12 regardless of treatment duration. Five participants in the variable-duration arm and five in the fixed-duration arm experienced serious adverse events (p = 0.69), as did five participants receiving ribavirin and five participants receiving no ribavirin. CONCLUSIONS: SVR12 rates were significantly higher when ultrashort treatment varied between 4 and 7 weeks, rather than between 4 and 6 weeks. We found no evidence of ribavirin significantly affecting first-line SVR12, with unsuccessful first-line short-course therapy also not compromising subsequent retreatment with sofosbuvir, ledipasvir and ribavirin. FUTURE WORK: A priority for future work needs to be the development and evaluation of robust predictive measures to identify those patients who can be cured with ultrashort courses of therapy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN37915093, EudraCT 2015-005004-28 and CTA 19174/0370/001-0001. FUNDING: This project was funded by the Efficacy and Mechanism Evaluation programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 17. See the NIHR Journals Library website for further project information. Twit Text FOAVip Variable short duration treatment versus standard treatment, with and without adjunctive ribavirin, for chronic hepatitis C: the STOP-HCV-1 non-inferiority, factorial RCT????Variable short duration treatment versus standard treatment, with and without adjunctive ribavirin, for chronic hepatitis C: the STOP-HCV-1 non-inferiority, factorial RCT-/-Efficacy and Mechanism Evaluation http://www.kidney.de/pget.php?&tw=1&pmid=34723451 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34723451 #FOAvip English Wikipedia <ref>{{Cite pmid|34723451}}</ref> Variable short duration treatment versus standard treatment, with and without adjunctive ribavirin, for chronic hepatitis C: the STOP-HCV-1 non-inferiority, factorial RCT #MMPMID34723451 Cooke GS; Pett S; McCabe L; Jones C; Gilson R; Verma S; Ryder SD; Collier JD; Barclay ST; Ala A; Bhagani S; Nelson M; Ch'Ng CL; Stone B; Wiselka M; Forton D; McPherson S; Halford R; Nguyen D; Smith D; Ansari MA; Ainscough H; Dennis E; Hudson F; Barnes EJ; Walker AS Variable short duration treatment versus standard treatment, with and without adjunctive ribavirin, for chronic hepatitis C: the STOP-HCV-1 non-inferiority, factorial RCT-/-Efficacy and Mechanism Evaluation 2021[Oct]; ä (ä): ä PMID34723451show ga BACKGROUND: High cure rates with licensed durations of therapy for chronic hepatitis C virus suggest that many patients are overtreated. New strategies in individuals who find it challenging to adhere to standard treatment courses could significantly contribute to the elimination agenda. OBJECTIVES: To compare cure rates using variable ultrashort first-line treatment stratified by baseline viral load followed by retreatment, with a fixed 8-week first-line treatment with retreatment with or without adjunctive ribavirin. DESIGN: An open-label, multicentre, factorial randomised controlled trial. RANDOMISATION: Randomisation was computer generated, with patients allocated in a 1 : 1 ratio using a factorial design to each of biomarker-stratified variable ultrashort strategy or fixed duration and adjunctive ribavirin (or not), using a minimisation algorithm with a probabilistic element. SETTING: NHS. PARTICIPANTS: A total of 202 adults (aged >/= 18 years) infected with chronic hepatitis C virus genotype 1a/1b or 4 for >/= 6 months, with a detectable plasma hepatitis C viral load and no significant fibrosis [FibroScan((R)) (Echosens, Paris, France) score F0-F1 or biopsy-proven minimal fibrosis], a hepatitis C virus viral load < 10,000,000 IU/ml, no previous exposure to direct-acting antiviral therapy for this infection and not pregnant. Patients co-infected with human immunodeficiency virus were eligible if human immunodeficiency virus viral load had been < 50 copies/ml for > 24 weeks on anti-human immunodeficiency virus drugs. INTERVENTIONS: Fixed-duration 8-week first-line therapy compared with variable ultrashort first-line therapy, initially for 4-6 weeks (continuous scale) stratified by screening viral load (variable ultrashort strategy 1, mean 32 days of treatment) and then, subsequently, for 4-7 weeks (variable ultrashort strategy 2 mean 39 days of duration), predominantly with ombitasvir, paritaprevir, ritonavir (Viekirax((R)); AbbVie, Chicago, IL, USA), and dasabuvir (Exviera((R)); AbbVie, Chicago, IL, USA) or ritonavir. All patients in whom first-line treatment was unsuccessful were immediately retreated with 12 weeks' sofosbuvir, ledipasvir (Harvoni((R)), Gilead Sciences, Inc., Foster City, CA, USA) and ribavirin. MAIN OUTCOME MEASURE: The primary outcome was overall sustained virological response (persistently undetectable) 12 weeks after the end of therapy (SVR12). RESULTS: A total of 202 patients were analysed. All patients in whom the primary outcome was evaluable achieved SVR12 overall [100% (197/197), 95% confidence interval 86% to 100%], demonstrating non-inferiority between fixed- and variable-duration strategies (difference 0%, 95% confidence interval -3.8% to 3.7%, prespecified non-inferiority margin 4%). A SVR12 following first-line treatment was achieved in 91% (92/101; 95% confidence interval 86% to 97%) of participants randomised to the fixed-duration strategy and by 48% (47/98; 95% confidence interval 39% to 57%) allocated to the variable-duration strategy. However, the proportion achieving SVR12 was significantly higher among those allocated to variable ultrashort strategy 2 [72% (23/32), 95% confidence interval 56% to 87%] than among those allocated to variable ultrashort strategy 1 [36% (24/66), 95% confidence interval 25% to 48%]. Overall, a SVR12 following first-line treatment was achieved by 72% (70/101) (95% confidence interval 65% to 78%) of patients treated with ribavirin and by 68% (69/98) (95% confidence interval 61% to 76%) of those not treated with ribavirin. A SVR12 with variable ultrashort strategies 1 and 2 was 52% (25/48) (95% confidence interval 38% to 65%) with ribavirin, compared with 44% (22/50) (95% confidence interval 31% to 56) without. However, at treatment failure, the emergence of viral resistance was lower with ribavirin [12% (3/26), 95% confidence interval 2% to 30%] than without [38% (11/29), 95% confidence interval 21% to 58%; p = 0.01]. All 10 individuals who became undetectable at day 3 of treatment achieved first-line SVR12 regardless of treatment duration. Five participants in the variable-duration arm and five in the fixed-duration arm experienced serious adverse events (p = 0.69), as did five participants receiving ribavirin and five participants receiving no ribavirin. CONCLUSIONS: SVR12 rates were significantly higher when ultrashort treatment varied between 4 and 7 weeks, rather than between 4 and 6 weeks. We found no evidence of ribavirin significantly affecting first-line SVR12, with unsuccessful first-line short-course therapy also not compromising subsequent retreatment with sofosbuvir, ledipasvir and ribavirin. FUTURE WORK: A priority for future work needs to be the development and evaluation of robust predictive measures to identify those patients who can be cured with ultrashort courses of therapy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN37915093, EudraCT 2015-005004-28 and CTA 19174/0370/001-0001. FUNDING: This project was funded by the Efficacy and Mechanism Evaluation programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 17. See the NIHR Journals Library website for further project information. äVariable short duration treatment versus standard treatment, with and (epmc).pdf DeepDyve Pubget Overpricing