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Safety and Efficacy of Raltegravir+TDF+3TC in HBV/HIV Co-infected Patients

This study is not yet open for participant recruitment.
Verified March 2011 by Yunnan AIDS Care Center
Sponsor:
Information provided by:
Yunnan AIDS Care Center
ClinicalTrials.gov Identifier:
NCT01318096
First received: March 8, 2011
Last updated: March 17, 2011
Last verified: March 2011
History of Changes
  Purpose

In this pilot study, the investigators would examine the safety and efficacy of integrase inhibitor-Raltegravir in the control of HIV/HBV co-infection.


Condition Intervention
HBV Coinfection
HIV Infections
 Drug: raltegravir and tenofovir and lamivudine
Drug: efavirenz+tenofovir+lamivudine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Pilot Estimation Study to Compare the Safety and Efficacy of Raltegravir+TDF+3TC Versus TDF+3TC+EFV in HBV/HIV Co-infected Patients

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Further study details as provided by Yunnan AIDS Care Center:

Primary Outcome Measures:
  • Frequency and severity of adverse events [ Time Frame: In 48 weeks (from baseline to study completion at 48 weeks) ] [ Designated as safety issue: Yes ]
    The investigators will collect the adverse events at every follow-up, and record them in CRFs. All AEs during the study will be analyzed according to the type, frequency and severity.


Secondary Outcome Measures:
  • Change of plasma HIV-1 RNA levels [ Time Frame: week 0,24 and 48 ] [ Designated as safety issue: No ]
  • Change of Peripheral blood CD4 cell counts [ Time Frame: week 0,4,8,12,24,36 and 48 ] [ Designated as safety issue: No ]
  • Change of plasma HBV-DNA levels [ Time Frame: week 0,12,24,36,and 48 ] [ Designated as safety issue: No ]
  • Change of serum total bilirubin levels（TBI） [ Time Frame: week 0,2,4,8,12,24,36 and 48 ] [ Designated as safety issue: Yes ]
  • Proportion of subjects with HBeAg seroconversion (HBeAg loss and presence of anti HBe) [ Time Frame: week 0,12,24,36,and week 48 ] [ Designated as safety issue: No ]
  • Emergence of drug resistance mutations, if appropriate [ Time Frame: week 0, 24 and 48 ] [ Designated as safety issue: No ]
  • Paired liver biopsy comparison according to inflammatory activity and fibrosis score [ Time Frame: week 0 and 48 ] [ Designated as safety issue: No ]
  • Change of serum alanine aminotransferase levels (ALT) [ Time Frame: week 0,2,4,8,12,24,36 and 48 ] [ Designated as safety issue: Yes ]
  • Change of serum aspartate aminotransferase levels (AST) [ Time Frame: week 0,2,4,8,12,24,36 and 48 ] [ Designated as safety issue: Yes ]
  • Change of blood urine nitrogen levels (BUN) [ Time Frame: week 0,2,4,8,12,24,36 and 48 ] [ Designated as safety issue: Yes ]
  • Change of serum creatinine levels (SCr) [ Time Frame: week 0,2,4,8,12,24,36 and 48 ] [ Designated as safety issue: Yes ]
  • Change of blood haemoglobin levels (HB) [ Time Frame: week 0,2,4,8,12,24,36 and 48 ] [ Designated as safety issue: Yes ]
  • Change of white blood cell counts (WBC) [ Time Frame: week 0,2,4,8,12,24,36 and 48 ] [ Designated as safety issue: Yes ]
  • Change of blood platelet counts (PLT) [ Time Frame: week 0,2,4,8,12,24,36 and 48 ] [ Designated as safety issue: Yes ]
  • Change of urine protein levels [ Time Frame: week 0,2,4,8,12,24,36 and 48 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: March 2011
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A:Raltegravir + tenofovir+lamivudine Drug: raltegravir and tenofovir and lamivudine
raltegravir 400mg BID and tenofovir 300mg qd and lamivudine 300mg gd for 48 weeks
Other Name: raltegravir: Isentress
Active Comparator: B:Efavirenz+tenofovir+lamivudine Drug: efavirenz+tenofovir+lamivudine
efavirenz 600mg QN +tenofovir 300mg qd +lamivudine 300mg qd for 48 weeks
Other Name: efavirenz: Sustiva

Detailed Description:

There are in total more than 72939 HIV infected people reported in Yunnan, the largest number for any province in China. About 800 HIV inpatients are admitted to our hospital every year, amongst them about 10% co-infected with HBV. HIV and HBV co-infection patients must receive two drugs active against both HIV and HBV, for example Tenofovir disoproxil fumarate (TDF)+ lamivudine (3TC) or TDF+FTC. TDF and 3TC are nucleotide analogues that can inhibit both HIV and HBV DNA polymerases (Dore, Cooper et al. 2004). Combination therapy could decrease drug resistance. In China, TDF is a second-line drug of the national free ART program; however FTC is not in the list of free drugs. There is likely higher risk of causing drug resistance in treating HBV or HIV infection with 3TC or TDF monotherapy than combination therapy.

Raltegravir inhibits the catalytic activity of HIV-1 integrase, and does not significantly inhibit human phosphoryl transferases including DNA polymerases α, β, and γ, and may have less adverse effects. In chronic HBV infection, HBV-DNA does integrate into human DNA which results in difficulty eradicating HBV from the patient's body.

In this pilot study, the investigators would examine the safety and efficacy of integrase inhibitor-Raltegravir in the control of HIV/HBV co-infection.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ability and willingness to provide written informed consent
  • HIV-1 infection, documented in patient medical record. Acceptable forms of documentation include positive HIV antibody or detectable HIV RNA
  • HIV-1 antiretroviral therapy naïve
  • Chronic HBV infection, defined as HBsAg positive >6 months. Both HBeAg positive and negative subjects will be eligible
  • Detectable HBV DNA ( > 300 copies/ml)
  • Serum alpha-fetoprotein (AFP) of ≤ 50 ng/ml within 4 weeks of study entry, or if elevated > 50 ng/ml, an imaging study demonstrating no evidence of hepatic tumor within 4 weeks of enrollment

Exclusion Criteria:

  • Allergy or sensitivity to study drug
  • Pregnancy, breastfeeding or unwillingness/inability to adhere to contraceptive methods for the duration of the study (Female study volunteers must not participate in a conception process (e.g., active attempt to become pregnant). If participating in sexual activity that could lead to pregnancy, the female study volunteer must use the following forms of contraception while receiving study-specific medication(s) and for 30 days after stopping the medication. One of the following methods MUST be used appropriately: (1)Condoms* (male or female) with or without a spermicidal agent; (2)Diaphragm or cervical cap with spermicide; (3)IUD; (4)Hormonal-based method.Condoms are recommended because their appropriate use is the only contraception method effective for preventing HIV transmission.
  • Prisoners or subjects who are incarcerated
  • Receipt of the following drugs with anti-HBV activity within 90 days prior to study entry or anticipated receipt during the course of the study including: ADV, telbivudine, alpha interferon, and other investigational agents with anti-HBV activity
  • Active opportunistic infection
  • Other causes of chronic liver disease identified (autoimmune hepatitis, haemochromatosis, Wilsons disease, alfa-1-antitrypsin deficiency)
  • Concurrent malignancy requiring cytotoxic chemotherapy
  • Decompensated or Child's C cirrhosis
  • Any other condition which in the opinion of the investigator might interfere with compliance or outcome of the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01318096

Locations
China, Yunnan Provice
Yunnan Provincial Hospital of Infectious Diseases/Yunnan AIDS Care Center Not yet recruiting
Kunming, Yunnan Provice, China, 650301
Contact: Cheng Xi Wang, M.D.     86 871 8728060     wxch62597@foxmail.com    
Principal Investigator: Cheng Xi Wang, M.D.            
Sponsors and Collaborators
Yunnan AIDS Care Center
Investigators
Principal Investigator: Cheng Xi Wang, M.D. Yunnan Provincial Hospital of Infectious Diseases/Yunnan AIDS Care Center
  More Information

No publications provided

Responsible Party: Xi-cheng Wang, Yunnan Provincial Hospital of Infectious Diseases/Yunnan AIDS Care Center
ClinicalTrials.gov Identifier: NCT01318096     History of Changes
Other Study ID Numbers: MSD-38154
Study First Received: March 8, 2011
Last Updated: March 17, 2011
Health Authority: China: State Food and Drug Administration

Keywords provided by Yunnan AIDS Care Center:
safety
efficacy
raltegravir
HBV/HIV co-infection

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Hepatitis B
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Viral, Human
 Hepatitis
Liver Diseases
Digestive System Diseases
Lamivudine
Tenofovir
Tenofovir disoproxil
Efavirenz
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on February 28, 2013