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Can you be dropped from trial because of high bilirubin?

I am in week 6 of my clinical trial with some of the new oral drugs from Abbot (AbbVie) as well as ribavirin. Last week, I got a panic call from my research nurse that I had to get new blood work because my bilirubin was too high. I have Gilbert's Syndrome, in addition to my Hep C. and cirrhosis, so my bilirubin typically runs high anyway. I took new labs and they came in at over 5 for my bilirubin. Other than the typical side effects of these drugs (headache, some fatigue), I don't feel any different. However, it seems that I am at risk at being dropped from the trial because of my high bilirubin. I wrote a letter to the nurse and to Abbott and I'm still in the trial, but I'm wondering if the effects of high bilirubin are something I should worry about and if I'm still in danger of being dropped by the trial? I just went undetectable, so I don't want to stop now! Does anyone have any good ways to bring down bilirubin? I've heard coffee enemas work, but I haven't been rushing to try them!
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CROI 2013: AbbVie Interferon-free Combos Cure Most Newly Treated Hepatitis C Patients


    Category: Experimental HCV Drugs
    Published on Friday, 15 March 2013 00:00
    Written by Liz Highleyman


HCV © Russell Kightley

All-oral regimens containing the HCV protease inhibitor ABT-450, a non-nucleoside polymerase inhibitor, and ribavirin led to sustained response for more than 90% of previously untreated patients -- including those with unfavorable IL28B gene patterns -- but only about half of prior non-responders, researchers reported at the 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013) last week in Atlanta.

Direct-acting antiviral agents that target various steps of the hepatitis C virus (HCV) lifecycle have brought about a new treatment paradigm for chronic hepatitis C, and many patients and clinicians are eagerly awaiting all-oral regimens without interferon.

Eric Lawitz from the University of Texas Health Science Center and colleagues compared various interferon-free combinations of direct-acting drugs being developed by AbbVie (formerly Abbott).

All 12-week regimens included the once-daily HCV NS3/4A protease inhibitor ABT-450, boosted with ritonavir (Norvir) to achieve adequate levels in the body (ABT-450/r). They also included a non-nucleoside HCV NS5B polymerase inhibitor -- either ABT-072 taken once daily or ABT-333 taken twice daily -- and 1000-1200 mg/day weight-based ribavirin.

Lawitz presented combined data from 4 cohorts in 2 studies:

    Cohort 1 (n=11): 150/100 mg ABT 450/r + 400 mg ABT-072 + ribavirin in treatment-naive patients;
    Cohort 2 (n=19): 250/100 mg ABT-450/r + 100 mg ABT-333 + ribavirin in treatment-naive patients;
    Cohort 3 (n=14): 150/100 mg ABT-450/r + 100 mg ABT-333 + ribavirin in treatment-naive patients;
    Cohort 4 (n=17): 150/100 mg ABT-450/r + 100mg ABT-333 + ribavirin in prior partial or null responders.

About 70% of participants overall were men (though this varied from about one-half to 100% in different treatment arms), about 80% were white, and the average age was approximately 53 years. About 80% had more difficult-to-treat HCV subtype 1a. In Cohort 4, about 60% were prior partial responders (still-detectable HCV RNA at the end of previous interferon-based therapy) and the rest null responders (less than a 2-logdecline in HCV RNA). People with HIV and hepatitis B coinfection were excluded.

Enrollment in Cohort 1 was restricted to patients with the favorable IL28B CC gene pattern, which is associated with good interferon response; its role in interferon-free therapy is not yet clear. In Cohort 2 half had the CC pattern, about one-third had the CT (intermediate) pattern and about 10% were TT (least favorable). In Cohort 3 the CC and CT proportions were reversed. In Cohort 4 no one had the CC pattern (typical of non-responders) while about 70% were CT and 30% TT.


    In Cohort 1 -- the sole arm testing ABT-072 -- 91% of patients achieved sustained virological response, or undetectable HCV RNA at 24 weeks post-treatment (SVR24), while 2 people (18%) relapsed.
    In Cohort 2 (250/100 mg ABT-450/r) and Cohort 3 (150/100 mg ABT-450/r), SVR24 rates were 95% and 86%, respectively; Cohort 3 included 1 person who had sustained response at week 12 (SVR12) but relapsed before week 24.
    For the more challenging treatment-experienced participants in Cohort 4, the SVR24 rate fell to just 47%; looking further out to 48 weeks post-treatment, 6 people experienced viral breakthrough while on therapy and 3 relapsed after finishing treatment.
    Breaking out the results by IL28B pattern, among the treatment-naive participants SVR24 rates were 85% for people with the CC pattern and 100% for those with either CT or TT, demonstrating that IL28B has no impact on these interferon-free regimens; for non-responders, SVR24 rates were 50% for those with the CT pattern and 40% for those with TT.
    1 person who experienced viral breakthrough had a resistance mutation at NS3 protease position D168 at baseline, and almost everyone else with on-treatment breakthrough or post-treatment relapse showed such mutations at the time of treatment failure; NS5B polymerase mutations were more variable, often involving G554 or S556.
    All combinations were generally safe and well tolerated.
    The most common side-effects were fatigue, nausea, headache, and dizziness. About 13% had elevated bilirubin, which Lawitz explained was due to a known effect of ABT-450 on a bilirubin transporter protein in the liver.
    There were no serious adverse events or deaths, and just 1 person in Cohort 2 stopped treatment early due to side effects.
    Efficacy and side effects did not differ significantly between the 150 mg and 250 mg ABT-450 doses.

"We're in a state of a paradigm shift to the era of direct-acting antivirals," Lawitz said at an accompanying CROI press conference. "For those with mild-to-moderate disease, as timelines for approval [of direct-acting drugs] firm up, we're using interferon less and putting more people in the warehouse" to wait for interferon-free treatment.

www.hivandhepatitis.com › ... › Experimental HCV Drugs
3 Responses
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317787 tn?1473358451
If I were you I would try to get an appointment with the doctor to talk to him/her to find out in what way you would be removed from the trial.
No offense to the nurse but sometimes they aren't right and sometimes they say things they shouldn't.
Good luck to you, congratulations on getting to UND!
Helpful - 0
5359548 tn?1366988604
I assume since you are cirrohtic you are on Abbott Turquoise. Trial procedure moves slow at best. I would ask to speak to the doctor yourself and find out just what the problem is. Generally they already know what is producing these high numbers. Getting kicked off the trial after 6 weeks is not something they do just like that. They may reduce your Riba dose. Or they will refer you to see your own doc to find out the cause. It may just be that she was wrong in what she was referring to. You are in an open label trial so you are privy to your labs every 2 weeks. Just request them. See for yourself what is going on.  
Helpful - 0
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