|Methods||Study design: randomised clinical trial.|
Inclusion criteria: treatment-naive patients aged 18 to 65 years with chronic HCV genotype 1 infection. Additional inclusion criteria were serum HCV RNA level 10,000 IU/mL, absolute neutrophil count 1500 mm3, and platelet count 100,000 mm3. Liver fibrosis status had to have been documented within 18 months (no or minimal fibrosis, portal fibrosis, bridging fibrosis, or cirrhosis) with a liver biopsy or transient elastography.
Exclusion criteria: co-infection with human immunodeficiency virus or hepatitis B, any other cause of liver disease, poorly controlled diabetes mellitus (glycated haemoglobin value >8.5%), morbid obesity (weight >125 kg), severe depression or a severe psychiatric disorder, or active substance abuse.
Sample size calculation: yes.
|Participants||Study location: Europe - Austria, Belgium, France, Germany, Italy, Spain, The Netherlands.|
Total number of patients: 161.
Age: Group A 47.5, Group B 47.5 Group C 40.0, Group D 49.0.
Sex male n (%): Group A 20 (50.0%), Group B 20 (47.6%), Group C 21 (52.5%), Group D 19 (48.7%).
Previous HCV treatment: naive.
Histological findings n (%):
Cirrhosis: Group A 1 (2.5), Group B 1 (2.4), Group C 0, Group D 2 (5.1).
Bridging fibrosis: Group A 8 (20.0%), Group B 10 (23.8%), Group C 7 (17.5%), Group D 12 (30.8%).
Portal fibrosis: Group A 16 (40.0%), Group B 16 (38.1%), Group C 11 (27.5%), Group D 13 (33.3%).
No or minimal fibrosis: Group A 15 (37.5%), Group B 15 (35.7%), Group C 22 (55.0%), Group D 11 (28.2%).
< 800.000: Group A 10 (25.0%), Group B 8 (19.0%), Group C 7 (17.5%), Group D 5 (12.8%).
> 800.000: Group A 30 (75.0%), Group B 34 (81.0%), Group C 33 (82.5%), Group D 34 (87.2%).
|Interventions||Group A telaprevir 750 mg q8h plus peginterferon alfa-2a/ribavirin (q8h alfa-2a).|
Group B telaprevir 750 mg q8h plus peginterferon alfa-2b/ribavirin (q8h alfa-2b).
Group C telaprevir 1125 mg q12h plus peginterferon alfa-2a/ribavirin (q12h alfa-2a).
Group D telaprevir 1125 mg q12h plus peginterferon alfa-2b/ribavirin (q12h alfa-2b).
Peginterferon alfa-2a was administered at 180 μg/wk with ribavirin at 1000 to 1200 mg/day; peginterferon alfa-2b was administered at 1.5 μg/kg/wk1 with ribavirin at 800 to 1200 mg/day.
|Outcomes||Sustained virological response.|
|Notes||In the published article safety data has been presented only for the whole cohort (161 patients). It is not possible extract data regarding different treatment groups. Corresponding author has been contacted for further information regarding adverse events but no answer obtained.|
|Risk of bias|
|Bias||Authors' judgement||Support for judgement|
|Random sequence generation (selection bias)||Low risk||Comment: "The randomisation lists were generated by means of permuted blocks before the start of the trial, under the supervision of the sponsor".|
|Allocation concealment (selection bias)||Low risk||Comment: Central allocation before the star of the trial under supervision of the sponsor.|
|Blinding (performance bias and detection bias) |
|High risk||Comment: "Because this was an open label trial, blinding procedures were not applicable".|
|Incomplete outcome data (attrition bias) |
|Low risk||Comment: 79.5% of patients completed the treatment, but intention-to-treat analysis, worst-case scenario, was adopted and all patients have been included in final analysis.|
|Selective reporting (reporting bias)||Low risk||Comment: All clinically relevant and reasonably expected outcomes were reported. Study protocol registered in ClinicalTrials.gov (NCT00528528).|
|Other bias||High risk||Quote: "This clinical trial was funded by Janssen Pharmaceuticals, and by Vertex Pharmaceuticals Inc. The study sponsor was involved in the trial design and conduct, data collection, and data analysis. Several authors are employees of the sponsor".|