NIH Clinical Research Studies

Protocol Number: 01-I-0194

Active Accrual, Protocols Recruiting New Patients

Title:
A Non-Randomized, Open label, Study to Assess Hepatitis C Viral Kinetics in Predicting the Clinical Response in Patients with Hepatitis C Infection Coinfected with HIV-1 Treated with Peginterferon Alpha-2b and Ribavirin
Number:
01-I-0194
Summary:
This study will evaluate the safety and effectiveness of combination therapy with peginterferon alpha-2b and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. In studies of patients with hepatitis C alone, interferon alpha-2b plus ribavirin treatment eradicated the HCV in almost half the patients. Peginterferon alpha-2b is a compound that results from attaching a polyethylene glycol molecule to interferon alpha-2b. This compound stays in the blood longer than unmodified interferon alpha-2b, causing a higher blood concentration and thus maintaining activity against the hepatitis C virus.

HIV-infected patients 21 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 will be screened with blood and urine tests and possibly a liver biopsy, if a recent one is not available. The liver biopsy is done to determine the severity of liver disease. For this test, patients are admitted to the NIH Clinical Center for 1 to 2 days. A sedative is injected into an arm vein, 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. A chest X-ray, electrocardiogram (EKG) and liver ultrasound are also done. Within 4 weeks of the screening tests, candidates who appear eligible for the study will have a physical examination, medical history and repeat blood tests. Women who can become pregnant will have serial pregnancy tests throughout the study.

Patients who meet the study criteria and decide to participate will begin treatment with weekly injections under the skin of peginterferon alpha-2b and take ribavirin pills twice a day by mouth. In addition, patients will continue to take all other medications prescribed by their doctor. Clinic visits will be scheduled as follows:

- Days 1, 3, 5, 7, 10 and 21 - Blood will be drawn for safety tests and to measure blood levels of HIV and HCV.

- Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 52, 56 and 64 - Blood and urine tests will be done to determine the side effects of treatment and its effect on the HCV infection.

- Week 48 or end of treatment - Treatment will stop after 48 weeks. At this time, or earlier for those who do not complete the 48 weeks, patients will return to the clinic for a routine clinic visit, blood tests (including tests for hepatitis B and D) and abdominal ultrasound. Patients will be hospitalized for 2 days for a repeat liver biopsy.

- Week 72 and extended follow-up visits - At week 72, patients will return for blood tests and a routine clinic visit. HCV viral load will be measured. Follow-up visits every 3 months for an additional year will include a blood test to measure HCV viral load and a complete physical examination.

Sponsoring Institute:
National Institute of Allergy and Infectious Diseases (NIAID)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Male & Female
Referral Letter Required: No
Population Exclusion(s): Children

Eligibility Criteria:
INCLUSION CRITERIA:

Age greater than or equal to 18 years

Documentation of HIV-1 infection by any licensed ELISA test and confirmed by a Western Blot.

Documentation of Hepatitis C infection by demonstration of a positive test for hepatitis C antibody.

HCV RNA level greater than 2000 IU/ml by bDNA.

Histopathologic features consistent with chronic hepatitis C on liver biopsy at the time of enrollment.

Patients with CD4 greater than 100 cells/mm(3).

Ability to sign informed consent and willingness to comply with the study requirements and clinic policies.

Serum creatinine less than 1.5 mg/dL.

Serum phosphorus greater than or equal to 2.2 mg/dL (normal range NIH 2.3-4.3 mg/dL).

Neutrophil count greater than or equal to 1000 cells/mm(3).

Platelets greater than or equal to 75,000/mm(3).

Hemoglobin greater than or equal to 8.0 mg/dL.

ALT less than 7 times the NIH upper limit of normal.

Serum lipase less than 1.5 times 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 capable of pregnancy: use of effective contraception during study: effective contraception 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 OP8 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.

Ability to learn how to safely inject medication subcutaneously.

EXCLUSION CRITERIA:

PT-INR (in the absence of anti-cardiolipin antibody) prolonged by greater than 2 seconds.

Organ transplant recipient.

Elevated alpha-fetoprotein level (greater than 100 ng/mL).

Coexisting neoplastic disease requiring cytotoxic therapy.

Severe cardiac or pulmonary decompensation.

Severe liver decompensation or advanced cirrhosis patients.

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.

Severe retinopathy.

Hemoglobinopathy

Direct bilirubin more than or equal to 2 times ULN.

No patients 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 160) except history of drug-associated hepatitis with discontinuation of the causative agent.

Hepatic mass suggestive of hepatocellular carcinoma.

Current alcohol or substance abuse that potentially could interfere with patient compliance.

Significant heart failure.

Evidence 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.

Currently taking didanosine (ddl or Videx-EC or Videx) as part of antiretroviral regimen.

Special Instructions: Currently Not Provided
Keywords:
Liver Disease
Virologic Response
Immune Mechanisms
Cirrhosis
Eradication
Recruitment Keywords:
HIV
Hepatitis C
Conditions:
Hepatitis C
HIV Infections
Investigational Drug(s):
None
Investigational Device(s):
None

Contacts:
Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:
Early hepatitis C virus-RNA responses predict interferon treatment outcomes in chronic hepatitis c

Long-term mortality after transfusion associated non-A, non-B hepatitis

The epidemiology of viral hepatitis in the United States

Active Accrual, Protocols Recruiting New Patients

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