TriangleNCT00529568 · CITED IN SOURCE DOCUMENTS
Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Benefit Subjects With Hepatitis C Liver Disease
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2013-11-05
The purpose of this study is to assess the ability of eltrombopag to maintain a platelet count sufficient to facilitate initiation of antiviral therapy, to minimise antiviral therapy dose reductions and to avoid permanent discontinuation of antiviral therapy. The clinical benefit of eltrombopag will be measured by the proportion of subjects who are able to achieve a Sustained Virological Response (SVR).
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Number of Participants With Sustained Virologic Response (SVR) in the Double-blind (DB) Antiviral Treatment Phase
Number of Participants Whose Platelet Count Increased From a Baseline Count of <75 Gi/L to a Count Greater Than or Equal to (>=) 100 Giga (10^9) Cells Per Liter (Gi/L) During the Open-label (OL) Pre-Antiviral Treatment Phase
Number of Participants Receiving the Indicated Doses of Eltrombopag in the OL Phase Who Initiated Antiviral Therapy (Peginterferon Alfa-2a and Ribavirin) in the DB Phase
Median Platelet Count at the Indicated Time Points During the OL Phase
Median Platelet Count at the Indicated Time Points During the DB Phase
Number of Participants in the Indicated Categories for Minimum Platelet Count With Antiviral Therapy
Number of Participants With Rapid Virological Response (RVR) and Extended RVR (eRVR) During the DB Phase
Number of Participants With Early Virological Response (EVR) and Complete EVR (cEVR) During the DB Phase
Number of Participants With End of Treatment Response (ETR) and Sustained Virological Response at Week 12 of Follow-up (SVR12) During the DB Phase
Number of Participants in the Indicated Categories for Antiviral Therapy Dose Reductions in the DB Phase
Time to First Dose Reduction of Peginterferon Alfa-2a and Ribavirin Therapy in the DB Phase
Number of Participants With the Indicated Levels of Peginterferon Dose Reductions in the DB Phase
Number of Participants Who Prematurely Discontinued Antiviral Therapy in the DB Phase
Number of Participants Categorized as Responders (R) and Non-responders (NR) for SVR and RVR to Antiviral Therapy in the Indicated Variants of Interleukin 28B (IL28B) (or Interferon, Lambda 3)
Number of Participants With the Indicated Shift From Baseline (BL) in Severity Grades for Clinical Chemistry Parameters (Calcium, Glucose [Glu.], Potassium [Pot.], and Sodium [Sod.]), Per Division of Acquired Immunodeficiency Syndrome (DAIDS)
Number of Participants With the Indicated Shifts From BL in Severity Grades for for Hematology Parameters (Hemoglobin, Lymphocytes [Lym.], Total Neutrophils [Tot Neu.], and White Blood Cells [WBC]), Per DAIDS
Number of Participants in the Indicated Categories for Cataract Event During the DB Phase, Per Clinical Events Committee (CEC) Adjudication
Number of Participants Assessed as Normal and Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at the Indicated Time Points During the DB Phase
Number of Participants With CS and NCS Change From Baseline for 12-lead ECG at the Indicated Time Points During the DB Phase
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points During the DB Phase
Mean Change From Baseline in Heart Rate at the Indicated Time Points During the DB Phase
Mean Change From Baseline in Weight at the Indicated Time Points During the DB Phase
Mean Change From Baseline in Body Mass Index (BMI) at the Indicated Time Points During the DB Phase
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: Male and female subjects, \>18 years Evidence of chronic hepatitis C virus (HCV) infection Subjects who are appropriate candidates for peginterferon (pegIFN) and ribavirin antiviral therapy A platelet count of \<75,000/mcL Haemoglobin \>11.0g/dL for men or \>10.0g/dL for women Absolute neutrophil count (ANC) \>750/mm3 and no history of infections associated with neutropenia Creatinine clearance \>50mL/minute All fertile males and females must use two forms of effective contraception between them during treatment and during the 24 weeks after treatment end Subject is able to understand, consent and comply with protocol requirements and instructions and is likely to complete the study as planned Exclusion criteria: Non-responders to previous treatment with pegIFN and ribavirin who failed to achieve a sustained virologic response (SVR) for reasons other than thrombocytopenia, despite an optimal course (dose and duration) of combination therapy with pegIFN and ribavirin Decompensated liver disease, e.g. Child-Pugh score \>6 or history of ascites or hepatic encephalopathy or current evidence of ascites Known hypersensitivity, intolerance or allergy to interferon (IFN), ribavirin, eltrombopag or any of their ingredients Serious cardiac, cerebrovascular, or pulmonary disease that would preclude treatment with pegIFN and ribavirin Subjects with a history of any one of the following: Suicide attempt or hospitalisation for depression in the past 5 years Any current severe or poorly controlled psychiatric disorder The following subjects are eligible for study participation, but must be assessed and followed (if recommended) by a mental health professional: * Subjects who have had a severe or poorly controlled psychiatric disorder more than 6 months ago but less than 5 years ago * Seizure disorder that has not been well controlled History of clinically significant bleeding from oesophageal or gastric varices Subjects with haemoglobinopathies, e.g. sickle cell anaemia, thalassemia major Any prior history of arterial or venous thrombosis AND two or more of the following risk factors: hereditary thrombophilic disorders (e.g. Factor V Leiden, ATIII deficiency, etc), hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension or cancer Pre-existing cardiac disease (New York Heart Association (NYHA) Grade III/IV), or arrhythmias known to involve the risk of thromboembolic events, or corrected QT interval (QTc) \>450 msec Evidence of hepatocellular carcinoma Laboratory evidence of infection with human immunodeficiency virus (HIV) or active Hepatitis B Virus (HBV) infection Any disease condition associated with active bleeding or requiring anticoagulation with heparin or warfarin Therapy with any anti-neoplastic or immuno-modulatory treatment \<6 months prior to the first dose of eltrombopag. Subjects who have had a malignancy diagnosed and/or treated within the past 5 years, except for subjects with localised basal or squamous cell carcinoma treated by local excision or subjects with malignancies who have been adequately treated and, in the opinion of the oncologist, have an excellent chance of cancer-free survival Pregnant or nursing women Males with a female partner who is pregnant History of alcohol/drug abuse or dependence within 6 months of the study start (unless participating in a controlled rehabilitation programme) Treatment with an investigational drug or IFN within 30 days or 5 half-lives (whichever is longer) of the screening visit History of platelet clumping that prevents reliable measurement of platelet counts History of major organ transplantation with an existing functional graft Thyroid dysfunction not adequately controlled Subjects planning to have cataract surgery Evidence of portal vein thrombosis on abdominal imaging within 3 months of the baseline visit
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- active treatment arm
- intervention Names
- Drug: eltrombopag
- label
- eltrombopag
- type
- EXPERIMENTAL
- description
- placebo control arm
- intervention Names
- Drug: placebo
- label
- placebo
- type
- PLACEBO_COMPARATOR
- interventions
- arm Group Labels
- eltrombopag
- description
- double-blind active treatment daily oral administation at dose of 25, 50, 75, or 100 mg
- name
- eltrombopag
- type
- DRUG
- arm Group Labels
- placebo
- description
- double-blind matched placebo control daily oral administration
- name
- placebo
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- DOUBLE
- who Masked
- PARTICIPANT
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 759
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Participants with SVR are defined as those with non-detectable Hepatitis C Virus (HCV) ribonucleic acid (RNA) at the end of treatment and all subsequent planned visits up to 24 weeks post-completion of the treatment period of the DB Phase.
- measure
- Number of Participants With Sustained Virologic Response (SVR) in the Double-blind (DB) Antiviral Treatment Phase
- time Frame
- From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
- secondary Outcomes
- description
- Participants were assessed for a shift from a baseline platelet count of \<75 Gi/L to a count \>=100 Gi/L during the OL Phase (up to 9 weeks). Local laboratories were used for platelet function tests. Platelet counts were measured by blood draw.
- measure
- Number of Participants Whose Platelet Count Increased From a Baseline Count of <75 Gi/L to a Count Greater Than or Equal to (>=) 100 Giga (10^9) Cells Per Liter (Gi/L) During the Open-label (OL) Pre-Antiviral Treatment Phase
- time Frame
- From Baseline up to Week 9 in the OL Phase
- description
- In the OL Phase, participants initially received the lowest dose of eltrombopag (25 mg QD) for 2 weeks. If after this time the platelet count was \<100 Gi/L, participants underwent sequential dose escalation to the next highest dose (50 mg QD for up to 2 weeks), with further dose escalations to 75 mg QD (up to 2 weeks) and 100 mg QD (up to a maximum of 3 weeks) if platelet counts remained \<100 Gi/L. Participants who achieved platelet counts \>=100 Gi/L when receiving any of the eltrombopag doses in the OL Phase initiated antiviral therapy in the DB Phase.
- measure
- Number of Participants Receiving the Indicated Doses of Eltrombopag in the OL Phase Who Initiated Antiviral Therapy (Peginterferon Alfa-2a and Ribavirin) in the DB Phase
- time Frame
- From Baseline up to Week 9 in the OL Phase
- description
- Blood taken from peripheral blood vessels was used for the measurement of platelet counts. The Last On Treatment assessment refers to the actual last treatment assessment, not necessarily to the End of Treatment assessment entered by the Investigator.
- measure
- Median Platelet Count at the Indicated Time Points During the OL Phase
- time Frame
- OL Phase: Baseline; Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, and 9; Antiviral Baseline (up to Week 10); End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 62); 12-week FU (up to Week 70); and 24-week FU (up to Week 82)
- description
- Blood taken from peripheral blood vessels was used for the measurement of platelet counts. The Last On Treatment assessment refers to the actual last treatment assessment, not necessarily to the End of Treatment assessment entered by the Investigator.
- measure
- Median Platelet Count at the Indicated Time Points During the DB Phase
- time Frame
- DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)
- description
- The minimum platelet count with antiviral therapy was categorized as follows: \<25 Gi/L; \>=25 to \<50 Gi/L; \>=50 to \<90 Gi/L; \>=90 to \<150 Gi/L; \>=150 Gi/L to \<200 Gi/L; \>=200 Gi/L to \<400 Gi/L; and \>=400 Gi/L.
- measure
- Number of Participants in the Indicated Categories for Minimum Platelet Count With Antiviral Therapy
- time Frame
- From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
- description
- RVR is defined as the absence of detectable HCV RNA after 4 weeks of antiviral treatment. eRVR is defined as the absence of detectable HCV RNA after 4 weeks of antiviral treatment that persisted through Week 12.
- measure
- Number of Participants With Rapid Virological Response (RVR) and Extended RVR (eRVR) During the DB Phase
- time Frame
- From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
- description
- EVR is defined as a clinically significant reduction from Baseline in HCV RNA (\>=2 log10 drop or undetectable) after 12 weeks of antiviral treatment. cEVR is defined as undetectable HCV RNA after 12 weeks of antiviral treatment.
- measure
- Number of Participants With Early Virological Response (EVR) and Complete EVR (cEVR) During the DB Phase
- time Frame
- From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
- description
- ETR is defined as the absence of detectable HCV RNA at the end of antiviral treatment. SVR12 is defined as the absence of detectable HCV RNA at the end of antiviral treatment and the 12-week follow-up assessment.
- measure
- Number of Participants With End of Treatment Response (ETR) and Sustained Virological Response at Week 12 of Follow-up (SVR12) During the DB Phase
- time Frame
- From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
- description
- Participants were assigned a score equal to the number of times their dose of antiviral therapy (peginterferon or ribavirin) was reduced (0=no dose reductions \[DRs\]; 1=one DR; 2=two DRs; 3=three DRs; \>3=more than three DRs). When possible, every effort was made to maintain the recommended dose of antiviral therapy for the treatment duration in the DB Phase. However, when dose modification of antiviral therapy was required due to safety concerns, it was performed by the Investigator as per the region-specific product labels of peginterferon and ribavirin.
- measure
- Number of Participants in the Indicated Categories for Antiviral Therapy Dose Reductions in the DB Phase
- time Frame
- From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
- description
- Time to first dose reduction was calculated as the time period from the first dose to the first dose reduction.
- measure
- Time to First Dose Reduction of Peginterferon Alfa-2a and Ribavirin Therapy in the DB Phase
- time Frame
- From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
- description
- The assigned dose in the DB Phase of peginterferon alfa-2a was 180 micrograms (µg). For peginterferon dose modification, downward adjustments in one-level increments were considered. The lowest dose of peginterferon alfa-2a that was allowed to be administered was 45 µg. When dose adjustment was required for moderate to severe adverse reactions (clinical and/or laboratory), an initial dose reduction to 135 µg was generally adequate. In some cases, a dose reduction to 90 µg or 45 µg was necessary. Dose increases toward the original dose were considered when the adverse reaction was resolved.
- measure
- Number of Participants With the Indicated Levels of Peginterferon Dose Reductions in the DB Phase
- time Frame
- From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
- description
- The following participants were considered to have discontinued antiviral therapy: participants who were lost to follow-up; participants who withdrew for any reason; participants who died; participants who otherwise did not complete their planned course of antiviral therapy for any reason. The planned duration of antiviral therapy was 48 weeks for participants with Non-Genotype 2/3 and 24 or 48 weeks for participants with Genotype 2/3.
- measure
- Number of Participants Who Prematurely Discontinued Antiviral Therapy in the DB Phase
- time Frame
- From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Full study description
- brief Summary
- The purpose of this study is to assess the ability of eltrombopag to maintain a platelet count sufficient to facilitate initiation of antiviral therapy, to minimise antiviral therapy dose reductions and to avoid permanent discontinuation of antiviral therapy. The clinical benefit of eltrombopag will be measured by the proportion of subjects who are able to achieve a Sustained Virological Response (SVR).
Source references
- references
- citation
- Saleh MI, Obeidat AR, Anter HA, Khanfar AA. Eltrombopag dose predictors in thrombocytopenic subjects with hepatitis C virus infection. Clin Exp Pharmacol Physiol. 2015 Oct;42(10):1030-5. doi: 10.1111/1440-1681.12451.
- pmid
- 26173631
- type
- DERIVED
- citation
- Giannini EG, Afdhal NH, Sigal SH, Muir AJ, Reddy KR, Vijayaraghavan S, Elkashab M, Romero-Gomez M, Dusheiko GM, Iyengar M, Vasey SY, Campbell FM, Theodore D. Non-cirrhotic thrombocytopenic patients with hepatitis C virus: Characteristics and outcome of antiviral therapy. J Gastroenterol Hepatol. 2015 Aug;30(8):1301-8. doi: 10.1111/jgh.12942.
- pmid
- 25777337
- type
- DERIVED
- citation
- Afdhal NH, Dusheiko GM, Giannini EG, Chen PJ, Han KH, Mohsin A, Rodriguez-Torres M, Rugina S, Bakulin I, Lawitz E, Shiffman ML, Tayyab GU, Poordad F, Kamel YM, Brainsky A, Geib J, Vasey SY, Patwardhan R, Campbell FM, Theodore D. Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy. Gastroenterology. 2014 Feb;146(2):442-52.e1. doi: 10.1053/j.gastro.2013.10.012. Epub 2013 Oct 12.
- pmid
- 24126097
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice