HIV InfectionsPhase 4NCT00661349
Trial About Hepatic Security of Antiretroviral Treatment Based on Kaletra Versus Nevirapine in Co-infected HIV/HCV Patients
A Phase 4 study testing Lopinavir/ritonavir and Nevirapine in people with HIV Infections, run by Germans Trias i Pujol Hospital at 9 sites in Spain.
Trial summary
In retrospective studies, acceleration of hepatic fibrosis has been seen in Nevirapine (NVP) treatment when compared with Protease Inhibitors (PI) boosted with ritonavir treatment in patients with Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) infection. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Lopinavir/ritonavir and Nevirapine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 9 sitesSpain
- Study dates
- Feb 2008to Dec 2008
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 18 years old or elder.
- HCV and HIV co-infected patients.
- Patients with antiretroviral treatment based in NVP plus 2 NRTIs (or 1 NRTI and Tenofovir), with undetectable viral load (under 50 copies/mL) during at least the last 24 weeks.
- If women and of childbearing age, negative pregnancy test. Furthermore, barrier contraceptive method must be undertaken during the study.
- Date and signature of the informed consent.
Who cannot join
- Concomitant treatment with drugs that can significantly interact with the study drugs.
- Opportunistic infections in the last 6 months.
- Patients who can be candidates for an HCV infection treatment in the next 3 years.
- Patients in who efficacy of previous NRTIs can not be ensured. For example, patients with mono or dual therapy history or with previous blips in whom NRTI-related mutations were identified that could reduce the sensibility to the used backbone.
- Active alcohol consumption (over 50 g per day) or other substance abuse.
- Pregnant or breastfeeding women.
Show all 9Show fewer
- Patients with transaminase level over 5 times the Upper Limit of Normality (ULN) or Creatinin over 2 mg/dL or Total Bilirubin over 3 times the ULN.
- Any formal contraindication for being treated with the study drugs.
- Patients who, basing in their antiretroviral treatment history, could be considered as being infected with a virus that has no sensibility to LPV.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Spain9 sites
Hospital General Universitario de Alicante
Alicante, 03010
H.U. Germans Trias i Pujol - Unitat VIH, Fundació Lluita contra la Sida
Badalona, Barcelona, 08916
Hospital Clínic i Provincial de Barcelona
Barcelona, 08036
Hospital Universitario Príncipe de Asturias
Madrid, 28005
Hospital Clínico San Carlos
Madrid, 28040
Hospital Universitario la Paz
Madrid, 28046
Hospital Son Dureta
Palma de Mallorca, Balearic Islands, 07014
Hospital Clínico de Salamanca
Salamanca, 37007
Hospital Universitario de Valme
Seville, 41014
About this study
Official title: Prospective, Open Label and Randomized Clinical Trial About Hepatic Security of Antiretroviral Treatment Based on Kaletra Versus Nevirapine in Co-infected HIV/HCV Patients
In retrospective studies, acceleration of hepatic fibrosis has been seen in Nevirapine (NVP) treatment when compared with Protease Inhibitors (PI) boosted with ritonavir treatment in patients with Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) infection. The high incidence in our country of HIV-HCV co-infection, the availability of a new Kaletra (LPV/r) formulation (more convenient and better tolerated than soft capsules) as well as the possibility of analyzing hepatic fibrosis evolution in a fast and bloodless way, make attractive a study that, in a prospective way, could check the benefits of substituting NVP by LPV/r on hepatic fibrosis in this community.
Read the detailed description
The prevalence of the HIV-HCV co-infection in Spain is one of the highest because both infections are strongly related to parenteral drugs use; so, from 61 to 69 % of HIV infected patients are also HCV infected.
Acute HCV infection is asymptomatic in 60 to 70% of cases, being the chronification the natural illness evolution. 20% of the patients will develop hepatic cirrhosis after 20 to 30 years of being infected by the HCV. In cirrhosis cases, the hepatocellular carcinoma appears in a rate of 2 to 4% per year, according to studies done with HCV mono-infected patients. Fibrosis progression depends basically on the duration of HCV infection and on the age of infection, but also on other factors, like gender (is faster in men), alcohol consumption (worst over 50 g per day) and HIV co-infection. Several epidemiologist studies have described the negative impact of HIV co-infection, accelerating the progression to cirrhosis and the hepatocarcinoma.
The Highly Active Antiretroviral Treatment (HAART) has a positive impact on survival on co-infected patients, although the three drug families used in HAART can cause hepatic toxicity in this group of patients. Hepatic toxicity appears in 5 to 20% of patients, being more serious and common, but not exclusive, in case of NVP treatment.
On their part, not all PI have the same hepatotoxic profile. An association between serious hepatotoxicity and ritonavir at full strength, indinavir and indinavir plus saquinavir boosted with ritonavir has been found.
As far as fibrosis is concerned, there are studies that show that in HIV/HCV co-infected patients PI-based regimens are associated with a lower progression to fibrosis, while the progression rate to cirrhosis is higher in NVP-based regimens, mainly in those patients with advanced hepatic fibrosis.
Hepatic biopsy is considered the reference test to assess hepatic fibrosis, nevertheless it is an invasive, painful and with a low but potentially serious risk for the patient's life. Moreover, the viability of a hepatic biopsy can be doubted due to sampling error or interobservation variability. For that reason, several biochemist tests have been developed to reflect the hepatic fibrosis extent or stage in a reliable way. Recently a hepatic rigidity measure through elastography has been presented as a non-invasive and very promising method to assess hepatic fibrosis.
- Conditions
- HIV Infections
- Being tested
- Lopinavir/ritonavir, Nevirapine
- Keywords
- Kaletra, Nevirapina, HCV chronic infection, Fibroscan, hepatic fibrosis, treatment experienced
- Medical subject headings
- HIV Infections, Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lopinavir/ritonavirDrug
2 ITIAN (o 1 ITIAN+TDF)+ lopinavir/ritonavir, 2 tablet 200/50 mg to 12 hours
NevirapineDrug
2 ITIAN (o 1 ITIAN+TDF)+ nevirapine, 2 tablet 200/50 mg to 12 hours
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Nevirapine Receives: Drug: Nevirapine |
| 2 | Experimental | Lopinavir/ritonavir Receives: Drug: Lopinavir/ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
The average of hepatic rigidity increase in each group. Hepatic rigidity will be measured in kilopascals through elastography (Fibroscan). Distribution of hepatic rigidity will be normalized by a logarithmic transformat
Measured: From Basal to 144 week (last visit) every 3 months
Secondary outcomes (6)
Virological and immunologic efficacy will be assessed through the proportion of patients with virological failure during the follow-up and the CD4 lymphocytes count of both treatment regimens.
Measured: From Basal to 144 week (last visit) every 3 months
The effect of both treatments in lipidic and glucidic metabolism will be assessed through the following variables: Total Cholesterol, HDL and LDL Cholesterol, Triglycerides and Glucose.
Measured: From Basal to 144 week (last visit) every 3 months
Higher than log 7.2 Kpa in patients with non-significant basal fibrosis (less than log 7.2 Kpa)
Measured: From Basal to 144 week (last visit) every 3 months
The security of each regimen will be studied through the proportion of patients who give up treatment because of adverse events and hepatic-related adverse events presence.
Measured: From Basal to 144 week (last visit) every 3 months
Toxicity will be determined depending on: Clinical History and Physical Examination; Coagulation, hemogram and chemistry tests, which will include: transaminase levels, GGT, alkaline phosphatase, bilirrubin, albumin, urea and creatinin
Measured: From Basal to 144 week (last visit) every 3 months
Mortality rate during the study will be evaluated.
Measured: From Basal to 144 week (last visit) every 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2008 (estimated)
- Study startFeb 2008
- Primary completionDec 2008
- Study completionDec 2008
Why it stopped: It has been impossible to achieve the number of patients defined by protocol
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Germans Trias i Pujol Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00661349
- Sponsor's protocol ID
- A10-174 (KANELA)
- Status last verified
- Dec 2019
- First submitted
- 10 Apr 2008
- Last updated
- 5 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Open Label and Randomized Clinical Trial About Hepatic Security of Antiretroviral Treatment Based on Kaletra Versus Nevirapine in Co-infected HIV/HCV Patients
- ClinicalTrials.gov ID
- NCT00661349
- Acronym / sponsor ID
- A10-174 (KANELA)
- Conditions
- HIV Infections
- Keywords
- Kaletra, Nevirapina, HCV chronic infection, Fibroscan, hepatic fibrosis, treatment experienced
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: It has been impossible to achieve the number of patients defined by protocol
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Germans Trias i Pujol HospitalUniversity, hospital or other
- Collaborators
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Study start
- Feb 2008
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 18 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In retrospective studies, acceleration of hepatic fibrosis has been seen in Nevirapine (NVP) treatment when compared with Protease Inhibitors (PI) boosted with ritonavir treatment in patients with Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) infection. The high incidence in our country of HIV-HCV co-infection, the availability of a new Kaletra (LPV/r) formulation (more convenient and better tolerated than soft capsules) as well as the possibility of analyzing hepatic fibrosis evolution in a fast and bloodless way, make attractive a study that, in a prospective way, could check the benefits of substituting NVP by LPV/r on hepatic fibrosis in this community.
Detailed description
The prevalence of the HIV-HCV co-infection in Spain is one of the highest because both infections are strongly related to parenteral drugs use; so, from 61 to 69 % of HIV infected patients are also HCV infected.
Acute HCV infection is asymptomatic in 60 to 70% of cases, being the chronification the natural illness evolution. 20% of the patients will develop hepatic cirrhosis after 20 to 30 years of being infected by the HCV. In cirrhosis cases, the hepatocellular carcinoma appears in a rate of 2 to 4% per year, according to studies done with HCV mono-infected patients. Fibrosis progression depends basically on the duration of HCV infection and on the age of infection, but also on other factors, like gender (is faster in men), alcohol consumption (worst over 50 g per day) and HIV co-infection. Several epidemiologist studies have described the negative impact of HIV co-infection, accelerating the progression to cirrhosis and the hepatocarcinoma.
The Highly Active Antiretroviral Treatment (HAART) has a positive impact on survival on co-infected patients, although the three drug families used in HAART can cause hepatic toxicity in this group of patients. Hepatic toxicity appears in 5 to 20% of patients, being more serious and common, but not exclusive, in case of NVP treatment.
On their part, not all PI have the same hepatotoxic profile. An association between serious hepatotoxicity and ritonavir at full strength, indinavir and indinavir plus saquinavir boosted with ritonavir has been found.
As far as fibrosis is concerned, there are studies that show that in HIV/HCV co-infected patients PI-based regimens are associated with a lower progression to fibrosis, while the progression rate to cirrhosis is higher in NVP-based regimens, mainly in those patients with advanced hepatic fibrosis.
Hepatic biopsy is considered the reference test to assess hepatic fibrosis, nevertheless it is an invasive, painful and with a low but potentially serious risk for the patient's life. Moreover, the viability of a hepatic biopsy can be doubted due to sampling error or interobservation variability. For that reason, several biochemist tests have been developed to reflect the hepatic fibrosis extent or stage in a reliable way. Recently a hepatic rigidity measure through elastography has been presented as a non-invasive and very promising method to assess hepatic fibrosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: NevirapineNevirapine |
| 2 | Experimental | Drug: Lopinavir/ritonavirLopinavir/ritonavir |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 18 years old or elder.
- HCV and HIV co-infected patients.
- Patients with antiretroviral treatment based in NVP plus 2 NRTIs (or 1 NRTI and Tenofovir), with undetectable viral load (under 50 copies/mL) during at least the last 24 weeks.
- If women and of childbearing age, negative pregnancy test. Furthermore, barrier contraceptive method must be undertaken during the study.
- Date and signature of the informed consent.
Key exclusion criteria (9 listed)
- Concomitant treatment with drugs that can significantly interact with the study drugs.
- Opportunistic infections in the last 6 months.
- Patients who can be candidates for an HCV infection treatment in the next 3 years.
- Patients in who efficacy of previous NRTIs can not be ensured. For example, patients with mono or dual therapy history or with previous blips in whom NRTI-related mutations were identified that could reduce the sensibility to the used backbone.
- Active alcohol consumption (over 50 g per day) or other substance abuse.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lopinavir/ritonavir2 ITIAN (o 1 ITIAN+TDF)+ lopinavir/ritonavir, 2 tablet 200/50 mg to 12 hours | Drug | 2 |
| Nevirapine2 ITIAN (o 1 ITIAN+TDF)+ nevirapine, 2 tablet 200/50 mg to 12 hours | Drug | 1 |
Primary outcome
The average of hepatic rigidity increase in each group. Hepatic rigidity will be measured in kilopascals through elastography (Fibroscan). Distribution of hepatic rigidity will be normalized by a logarithmic transformat
Time frame: From Basal to 144 week (last visit) every 3 months
6 secondary outcomes
Virological and immunologic efficacy will be assessed through the proportion of patients with virological failure during the follow-up and the CD4 lymphocytes count of both treatment regimens.
Time frame: From Basal to 144 week (last visit) every 3 months
The effect of both treatments in lipidic and glucidic metabolism will be assessed through the following variables: Total Cholesterol, HDL and LDL Cholesterol, Triglycerides and Glucose.
Time frame: From Basal to 144 week (last visit) every 3 months
Higher than log 7.2 Kpa in patients with non-significant basal fibrosis (less than log 7.2 Kpa)
Time frame: From Basal to 144 week (last visit) every 3 months
The security of each regimen will be studied through the proportion of patients who give up treatment because of adverse events and hepatic-related adverse events presence.
Time frame: From Basal to 144 week (last visit) every 3 months
Toxicity will be determined depending on: Clinical History and Physical Examination; Coagulation, hemogram and chemistry tests, which will include: transaminase levels, GGT, alkaline phosphatase, bilirrubin, albumin, urea and creatinin
Time frame: From Basal to 144 week (last visit) every 3 months
Mortality rate during the study will be evaluated.
Time frame: From Basal to 144 week (last visit) every 3 months
Results and safety
The study was stopped early (reason given: It has been impossible to achieve the number of patients defined by protocol). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lopinavir/ritonavir and Nevirapine in people with HIV Infections, run by Germans Trias i Pujol Hospital at 9 sites in Spain.
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 5 inclusion and 9 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: stopped early, as of the sponsor's last update on 5 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Spain. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: It has been impossible to achieve the number of patients defined by protocol). Results are not available in the source record.
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?
The average of hepatic rigidity increase in each group. Hepatic rigidity will be measured in kilopascals through elastography (Fibroscan). Distribution of hepatic rigidity will be normalized by a logarithmic transformat (time frame: From Basal to 144 week (last visit) every 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Dec 2019.