AzTrials
AzTrials

Hepatitis CPhase 2PIFNPKNCT00085917

Peginterferon Alpha-2a and Ribavirin to Treat Hepatitis C in HIV-infected Patients

A Phase 2 study testing Double dose pegylated interferon with weight based Ribavirin and standard dose pegylated interferon alfa -2a and ribavirin in people with Hepatitis C and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will evaluate the safety and effectiveness of combination therapy with peginterferon alpha-2a and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. Peginterferon alpha with ribavirin is the therapy of choice for people with HCV alone. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatitis C, HIV Infections
What is being tested?
Double dose pegylated interferon with weight based Ribavirin and standard dose pegylated interferon alfa -2a and ribavirin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteUnited States
Study dates
Jun 2004to Nov 2008
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age greater than or equal to18 years.
  • Documentation of HIV-1 infection by licensed ELISA test and confirmed by a Western Blot.
  • Documentation of Hepatitis C infection by demonstration of a positive test for hepatitis C antibody and on HCV RNA level of 2000 or greater.
  • Histopathologic features consistent with chronic hepatitis C on liver biopsy at the time of enrollment. A liver biopsy done for a subject within a year prior to his or her participation may be used as the baseline biopsy.
  • Patients with CD4+ cell count greater than 200 cells/mm3 or CD4+ cell percentage greater than 14%.
  • Ability to sign informed consent and willingness to comply with the study requirements and clinic policies.
Show all 17Show fewer
  • Serum phosphorus greater than or equal to 2.2 mg/dL and less than or equal to 4.4 (normal range NIH 2.3-4.3 mg/dL).
  • Neutrophil count greater than or equal to 1000 cells/mm3.
  • Platelets greater than or equal to 50,000/ mm3.
  • Hemoglobin greater than or equal to 10.5 mg/dL.
  • ALT less than 7 X the NIH upper limit of normal.
  • Serum lipase less than 1.5 X the NIH upper limit of normal.
  • Not pregnant or breast-feeding. Pregnancy test must be negative within two weeks prior to dosing with study medications.
  • If the patient is able to become pregnant then she must use two effective methods of contraception during the study. Effective contraceptive methods include abstinence, surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap or sponge, or use of hormonal contraception with an anti-HIV regimen that will not alter metabolism of hormonal contraception. This is advised on the basis of using ribavirin, which may have a potential teratogenic effect in pregnant women.
  • Need to have a primary doctor outside of OP8 or as part of the OP8 training clinic who will be taking care of the patients for their HIV infection and liver disease.
  • Willing to designate a person for durable power of attorney on the NIH form for medical research and medical care purposes at the NIH Clinical Center.
  • Able to learn to safely inject medication subcutaneously or be able to find another person or a clinic to inject for him/her.

Who cannot join

  • Patient should not be on other experimental therapies during their participation in this protocol.
  • Patients should not have used interferon or peginterferon previously for the treatment of hepatitis C
  • Liver histology which, in the opinion of Clinical center pathologist, is consistent with any other co-existent cause of chronic liver disease as defined as chronic hepatitis B with positive HBSag, autoimmune hepatitis with a positive ANA greater than 1 unit or positive anti mitochondrial antibody greater than 1 unit, cholestatic disease with persistent elevation of Alkaline phosphatase, primary biliary cirrhosis or sclerosing cholangitis, Wilson's disease, alpha-1-antitrypsin deficiency, steatohepatitis (alcohol or non alcoholic) with marked steatosis, many Mallory bodies, or extensive zone 3 periportal fibrosis.
  • Hemochromatosis or secondary iron overload as defined by (1) an elevated serum ferritin or an iron saturation (serum iron/IBC X 100%) of greater than 50% and (2) presence of 3+ or more stainable Iron on liver biopsy according to the study pathologist or a history of previous phlebotomy for Iron overload will undergo HFE genetic counseling and those with a positive HFE genetic test demonstrating homozygosity for C282Y and H63D are not eligible. Those who have compound heterozygosity to C282Y and H63D are also not eligible.
  • Child Turcotte Pugh score greater than 7.
  • PT-INR greater than 2 or history of hemophilia.
Show all 31Show fewer
  • Organ transplant recipient.
  • Creatinine clearance less than 50 mL/min.
  • Elevated alpha-fetoprotein level (greater than 100 ng/mL).
  • Coexisting neoplastic disease except for Kaposi's Sarcoma, any non-metastatic skin cancer that has been resected, non-metastatic cervical or anal cancer that has been resected.
  • Severe cardiac or pulmonary decompensation.
  • Severe psychiatric disorder that would interfere with the adherence to protocol requirements.
  • Preexisting autoimmune disorders including inflammatory bowel diseases, psoriasis, and optic neuritis.
  • Preexisting uncontrolled seizure disorder.
  • Preexisting pancreatitis.
  • Severe retinopathy as determined by the ophthalmologist.
  • Hemoglobinopathy.
  • Currently taking didanosine as part of antiretroviral regimen.
  • Direct bilirubin greater than 0.6 mg/dL.
  • Using long-term systemic corticosteroids, immunosuppressives, or cytotoxic agents within 60 days of enrollment into the trial.
  • Chronic viral hepatitis of any other etiology other than hepatitis C.
  • Active systemic infections other than hepatitis C and HIV.
  • Liver disease caused by reasons other than hepatitis C like HBV, HDV, Wilson's, hemochromatosis, autoimmune hepatitis (ANA greater than 1 unit) except history of drug-associated hepatitis with discontinuation of the causative agent.
  • Hepatic mass suggestive of hepatocellular carcinoma as detected by ultrasound scan.
  • Alcohol or substance abuse that potentially could interfere with patient compliance.
  • History of esophageal varices.
  • Any systemic illness that will make it unlikely that the subject will be able to return to NIH for the required study visits.
  • Evidence of gastrointestinal malabsorption or chronic nausea or vomiting.
  • Male partners of pregnant women.
  • Pregnant women.
  • Breastfeeding women.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Twice-Weekly Peginterferon Alpha 2a and Ribavirin Induction Therapy for Chronic Hepatitis C in Patients Who Are Coinfected With HIV-1

This study will evaluate the safety and effectiveness of combination therapy with peginterferon alpha-2a and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. Peginterferon alpha with ribavirin is the therapy of choice for people with HCV alone. Peginterferon alpha-2a is a compound that results from attaching a polyethylene glycol molecule to interferon alpha-2a. This compound stays in the blood longer than unmodified interferon alpha-2a, causing a higher blood concentration and thus maintaining greater activity against the hepatitis C virus.

HIV-infected patients 18 years of age and older with chronic hepatitis C infection and a viral load greater than 2000 copies/mL may be eligible for this 2-1/2 year study. Candidates are screened with a medical history and physical examination, blood and urine tests, eye examination, chest x-ray, electrocardiogram (EKG), liver ultrasound, and pregnancy test in women who are able to become pregnant. If a recent liver biopsy is not available, this test is done to determine the type and severity of liver disease. The patient is given a sedative before the procedure. Then, the skin in the area over the biopsy site is numbed with a local anesthetic and a needle is inserted rapidly into and out of the liver to obtain a small tissue sample. The patient remains in the hospital overnight for monitoring.

Read more

Participants begin treatment with injections under the skin of peginterferon alpha-2a and ribavirin pills by mouth on study day 0. Peginterferon is given either once or twice a week for 4 weeks and then once a week for 44 weeks. Ribavirin is given daily. In addition, patients continue to take all other medications prescribed by their doctor. Clinic visits are scheduled for the following procedures:

  • Days 1, 3, 4, 7, 10 and weeks 2, 3, and 4 - Blood tests for safety measures and to measure blood levels of HIV and HCV.
  • Weeks 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 - Blood and urine tests to determine the side effects of treatment and its effect on the HCV infection. In addition, eye examinations are done every 3 months, and pregnancy and thyroid function tests are done several times during the treatment period.
  • Week 48 or end of treatment - Treatment stops after 48 weeks. At this time, or earlier for those who do not complete the 48 weeks, patients return to the clinic for a chest x-ray, EKG, blood tests, and abdominal ultrasound. Patients are hospitalized for a repeat liver biopsy.
  • Weeks 52, 56, 64 and 72 - Blood and urine tests to determine the side effects of treatment and its effect on the HCV infection, and a urine pregnancy test in women.
Read the detailed description

Hepatitis C infection occurs in one-third of all HIV-infected individuals. Liver disease has become more significant among patients coinfected with HIV and HCV. Several studies have shown that coinfected individuals develop earlier and more severe liver disease. Pegylated interferon alpha with ribavirin has become the therapy of choice among people with HCV alone. This is a randomized controlled study to address the safety and efficacy of a 4 week induction therapy consisting of twice-weekly pegylated interferon alpha-2a and daily ribavirin on HIV-1 and hepatitis C coinfected individuals. Twenty-two patients who are infected with both HIV and HCV and who also have evidence of chronic hepatitis will be randomized to receive peginterferon alpha-2a either twice weekly or once weekly for four weeks. They will then continue with standard weekly peginterferon for 44 more weeks. The patients will receive standard daily dose of ribavirin during the entire 48 weeks. These patients will be monitored for peginterferon level, HCV viral load, HIV viral load and CD4 counts and undergo a baseline liver biopsy and another at the end of 72 weeks. The results of the study will enable us to better delineate the efficacy of twice weekly peginterferon induction therapy in suppressing the hepatitis C virus in the first 4 weeks of the therapy. Since viral suppression for hepatitis C in the early phase of the combination treatment has predictive values for long term eradication of the virus, a therapy that improves early viral suppression may improve the long term cure rate. This will be especially important given the current low cure rate of HCV among HIV coinfected individuals.

Being tested
Double dose pegylated interferon with weight based Ribavirin, standard dose pegylated interferon alfa -2a and ribavirin
Keywords
Pegasys, Ribavirin, Early Virological Response, Hepatitis C, HIV
Medical subject headings
Hepatitis C, HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Double dose pegylated interferon with weight based RibavirinDrug

    Also called Pegasys

    pegylated interferon alfa -2a 180ug/twice weekly and weight based ribavirin for 4 weeks then pegylated interferon alfa -2a 180ug/ weekly for the remainder of the treatment

  • standard dose pegylated interferon alfa -2a and ribavirinDrug

    Also called pegasys

    pegylated interferon alfa -2a 180ug weekly and weight based ribavirin for duration of the treatment

Study groups in NCT00085917
Study groupRoleWhat they receive
Standard dose armActive comparatorPegylated interferon alfa -2a STANDARD DOSE Pegasys 180ug/week
Receives: Drug: standard dose pegylated interferon alfa -2a and ribavirin
Double dose armExperimentalDouble dose pegylated interferon with weight based Ribavirin
Receives: Drug: Double dose pegylated interferon with weight based Ribavirin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Sustained Virologic Response (SVR)

    SVR [ Sustained virological response] SVR was defined as HCV RNA levels below the limit of detection 24 weeks after the end of treatment.

    Measured: 72 weeks

Secondary outcomes (2)

  1. Number of Participants With Normalization of Liver Enzymes

    normalization of liver enzymes :Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) Alanine aminotransferase (ALT): Normal 6 - 41 U/L Aspartate aminotransferase (AST) : Normal 9 - 34 U/L

    Measured: week 24, week 48, week 72

  2. Number of Participants With Adverse Events

    Adverse Events

    • Anemia, Neutropenia and Psychiatric adverse events

    Measured: 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jun 2004 (estimated)
  2. Study startJun 2004
  3. Primary completionNov 2008
  4. Study completionNov 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00085917
Sponsor's protocol ID
040187
Other IDs
04-I-0187
Acronym
PIFNPK
Status last verified
Jun 2011
First submitted
16 Jun 2004
Last updated
27 Jun 2011
Data monitoring committee
No

Publications

  • Alter MJ, Mast EE. The epidemiology of viral hepatitis in the United States. Gastroenterol Clin North Am. 1994 Sep;23(3):437-55.

    PubMed 7989088

  • Seeff LB, Buskell-Bales Z, Wright EC, Durako SJ, Alter HJ, Iber FL, Hollinger FB, Gitnick G, Knodell RG, Perrillo RP, et al. Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group. N Engl J Med. 1992 Dec 31;327(27):1906-11. doi: 10.1056/NEJM199212313272703.

    PubMed 1454085

  • Koretz RL, Abbey H, Coleman E, Gitnick G. Non-A, non-B post-transfusion hepatitis. Looking back in the second decade. Ann Intern Med. 1993 Jul 15;119(2):110-5. doi: 10.7326/0003-4819-119-2-199307150-00003.

    PubMed 8512159

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Double dose pegylated interferon with weight based Ribavirin and standard dose pegylated interferon alfa -2a and ribavirin in people with Hepatitis C and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jun 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Sustained Virologic Response (SVR) (time frame: 72 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00085917, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2011.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in