HIV InfectionsNCT00122590
Evaluation of Therapeutic Drug Monitoring of Protease Inhibitors on Virologic Success and Tolerance of Highly Active Antiretroviral Therapy (HAART)
A study testing nelfinavir, lopinavir/r and indinavir in people with HIV Infections, run by French National Agency for Research on AIDS and Viral Hepatitis at 1 site in France.
Trial summary
This Cophar2 study is a trial which evaluates repeated early therapeutic drug monitoring, from weeks 2 to 24, after the initiation of HAART including either indinavir/r, lopinavir/r or the new 625 mg formulation of nelfinavir twice-a-day (bid). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- nelfinavir, lopinavir/r and indinavir
- How many people
- 115 participants
- Where
- 1 siteFrance
- Study dates
- Jul 2002to Mar 2005
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients infected with HIV-1
- Needing an antiretroviral treatment according to standard of care
- HIV viral load greater than 1000 copies/ml
- Beginning a treatment containing a PI (indinavir with or without ritonavir, nelfinavir, lopinavir + ritonavir) and 2 reverse transcriptase inhibitors
- PI-naive
- Antiretroviral treatment-naive or already treated with reverse transcriptase inhibitors but if the viral genotypic test does not show more than 2 major mutations (including T215Y/F, Q151M, M184V/I, V75M/S, L74V) and if 3 nucleoside analogues are still active except for didanosine.
Who cannot join
- Pregnant women and nursing mothers
- Acute HIV infection
- Diabetes
- Renal insufficiency with creatinine clearance below 30 ml/min
- Cardiac insufficiency
- Hepatic insufficiency with TP below 60%
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- Treatment with known interactions with PI
- Chemotherapy against Kaposi's sarcoma, lymphoma, neoplasia
- Treatment containing interferon (INF) or interleukin-2 (IL2) or HIV- immune vaccine
- Treatment with hypolipemic drugs
- Laxative treatment
- Previous renal colic
- Diarrhoea with more than 5 stools/day since one week
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective Trial to Evaluate How Therapeutic Drug Monitoring of Protease Inhibitors Increases Virologic Success and Tolerance of HAART (ANRS 111 COPHAR2)
This Cophar2 study is a trial which evaluates repeated early therapeutic drug monitoring, from weeks 2 to 24, after the initiation of HAART including either indinavir/r, lopinavir/r or the new 625 mg formulation of nelfinavir twice-a-day (bid). If trough concentrations were out of the range given for each protease inhibitor (PI), the PI dose was adjusted.
Read the detailed description
Because of the large pharmacokinetic inter-patient variability of protease inhibitors (PI), therapeutic drug monitoring (TDM) of protease inhibitor (PI) has been proposed to improve efficacy and tolerance of PI-containing HAART. The objective of the Cophar2 trial is to evaluate the feasibility and the impact of an early therapeutic drug monitoring in PI-naive HIV-1 infected patients in order to warrant virological success and safety of HAART.
It is a prospective, open, multicenter trial with repeated early TDM (weeks 2, 8 or 16, 24) after the initiation of HAART including either indinavir/r (IDV), lopinavir/r (LPV) or the new 625 mg formulation of nelfinavir (NFV) bid. It was planned to include 99 PI-naïve HIV-1 infected patients over 18 years old, 33 for each PI. Concentrations were measured by HPLC in each center. If trough concentrations were out of the range of 150-500, 2500-7000 or 1500-5500 ng/ml for IDV, LPV and NFV respectively, the PI doses were adjusted possibly more than once during the first 24 weeks of follow-up. Adjustments were done by steps of one pill (200, 133/33 or 250 mg for IDV, LPV/r or NFV, respectively) bid. Failure of the strategy was defined by either two consecutive viral loads over 200 copies/ml between weeks 16 and 48, or a validated PI-related adverse event grade III or IV or a grade II diarrhoea or renal lithiasis. Patients without adverse events before week 16 were defined as assessable if they had at least the virological assessment of week 16.
- Conditions
- HIV Infections
- Being tested
- nelfinavir, lopinavir/r, indinavir, ritonavir
- Keywords
- protease inhibitors, nelfinavir, lopinavir, indinavir, Pharmacokinetics
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nelfinavirDrug
lopinavir/rDrug
indinavirDrug
ritonavirDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
treatment failure defined as viral load greater than 200 copies/ml between week 16 (W16) and week 48 (W48) (confirmed by 2 samples spiked at least 15 days apart but no more than 45 days after virological failure, assayed by 50 copies/ml method)
toxicity related to PI, defined as adverse event grade 3 or 4 with ANRS quotation, renal colic, diarrhoea grade 2, or cholesterolemia over 10 times the normal value
Secondary outcomes (12)
virological failure: viral load over 200 copies/ml between W16 and W48 (confirmed by 2 samples spiked at least 15 days apart but no more than 45 days after virological failure, assayed by 50 copies/ml method)
toxicity related to PI: adverse events grade 3 or 4 with ANRS quotation, renal colic, diarrhoea grade 2, or cholesterolemia over 10 times the normal value
patients with trough plasma concentrations outside the therapeutic range at W24 and W48
concentration changes with dosage variation
time to obtain a viral load below 200 copies/ml
relationship between adverse events grade 3 or 4 related to PI and plasma concentration at week 2 (W2)
relationship between pharmacokinetic parameters and/or plasma concentrations and the drop of viral load between day 0 (D0) and W2 and between D0 and week 4 (W4)
relationship between pharmacokinetic parameters and viral mutations occurring during the treatment of patients with virological failure (over 1000 copies/ml after week 24 [W24])
PI pharmacokinetic parameter estimation and evaluation of variability
pharmacokinetic variability of nucleoside analogues at W2
intracellular concentration of nucleoside triphosphate derivatives at W2 (trough and maximum) and relationship between virological response and adverse events
relationship between inhibitory quotient of indinavir and virological response
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2005 (estimated)
- Study startJul 2002
- Study completionMar 2005
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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 115 participants
Sponsor and investigators
- Lead sponsor
- French National Agency for Research on AIDS and Viral Hepatitis
- Sponsor type
- Other government
- Collaborators
- Hoffmann-La Roche
- Investigators
- Dominique Salmon, MD, Principal investigator, Service de Medecine Interne Hopital Cochin ParisFrance Mentre, MD, Study chair, Inserm EMI 03 57
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00122590
- Sponsor's protocol ID
- ANRS111 COPHAR 2
- Status last verified
- Jul 2005
- First submitted
- 20 Jul 2005
- Last updated
- 1 Aug 2005
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Trial to Evaluate How Therapeutic Drug Monitoring of Protease Inhibitors Increases Virologic Success and Tolerance of HAART (ANRS 111 COPHAR2)
- ClinicalTrials.gov ID
- NCT00122590
- Acronym / sponsor ID
- ANRS111 COPHAR 2
- Conditions
- HIV Infections
- Keywords
- protease inhibitors, nelfinavir, lopinavir, indinavir, Pharmacokinetics
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 115 participants
- Lead sponsor
- French National Agency for Research on AIDS and Viral HepatitisOther government
- Collaborators
- Hoffmann-La Roche
- Study start
- Jul 2002
- Study completion
- Mar 2005
- First posted
- 22 Jul 2005 (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.
This Cophar2 study is a trial which evaluates repeated early therapeutic drug monitoring, from weeks 2 to 24, after the initiation of HAART including either indinavir/r, lopinavir/r or the new 625 mg formulation of nelfinavir twice-a-day (bid). If trough concentrations were out of the range given for each protease inhibitor (PI), the PI dose was adjusted.
Detailed description
Because of the large pharmacokinetic inter-patient variability of protease inhibitors (PI), therapeutic drug monitoring (TDM) of protease inhibitor (PI) has been proposed to improve efficacy and tolerance of PI-containing HAART. The objective of the Cophar2 trial is to evaluate the feasibility and the impact of an early therapeutic drug monitoring in PI-naive HIV-1 infected patients in order to warrant virological success and safety of HAART.
It is a prospective, open, multicenter trial with repeated early TDM (weeks 2, 8 or 16, 24) after the initiation of HAART including either indinavir/r (IDV), lopinavir/r (LPV) or the new 625 mg formulation of nelfinavir (NFV) bid. It was planned to include 99 PI-naïve HIV-1 infected patients over 18 years old, 33 for each PI. Concentrations were measured by HPLC in each center. If trough concentrations were out of the range of 150-500, 2500-7000 or 1500-5500 ng/ml for IDV, LPV and NFV respectively, the PI doses were adjusted possibly more than once during the first 24 weeks of follow-up. Adjustments were done by steps of one pill (200, 133/33 or 250 mg for IDV, LPV/r or NFV, respectively) bid. Failure of the strategy was defined by either two consecutive viral loads over 200 copies/ml between weeks 16 and 48, or a validated PI-related adverse event grade III or IV or a grade II diarrhoea or renal lithiasis. Patients without adverse events before week 16 were defined as assessable if they had at least the virological assessment of week 16.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients infected with HIV-1
- Needing an antiretroviral treatment according to standard of care
- HIV viral load greater than 1000 copies/ml
- Beginning a treatment containing a PI (indinavir with or without ritonavir, nelfinavir, lopinavir + ritonavir) and 2 reverse transcriptase inhibitors
- PI-naive
Key exclusion criteria (13 listed)
- Pregnant women and nursing mothers
- Acute HIV infection
- Diabetes
- Renal insufficiency with creatinine clearance below 30 ml/min
- Cardiac insufficiency
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 |
|---|---|---|
| nelfinavir | Drug | – |
| lopinavir/r | Drug | – |
| indinavir | Drug | – |
| ritonavir | Drug | – |
Primary outcome
treatment failure defined as viral load greater than 200 copies/ml between week 16 (W16) and week 48 (W48) (confirmed by 2 samples spiked at least 15 days apart but no more than 45 days after virological failure, assayed by 50 copies/ml method)
toxicity related to PI, defined as adverse event grade 3 or 4 with ANRS quotation, renal colic, diarrhoea grade 2, or cholesterolemia over 10 times the normal value
12 secondary outcomes
virological failure: viral load over 200 copies/ml between W16 and W48 (confirmed by 2 samples spiked at least 15 days apart but no more than 45 days after virological failure, assayed by 50 copies/ml method)
toxicity related to PI: adverse events grade 3 or 4 with ANRS quotation, renal colic, diarrhoea grade 2, or cholesterolemia over 10 times the normal value
patients with trough plasma concentrations outside the therapeutic range at W24 and W48
concentration changes with dosage variation
time to obtain a viral load below 200 copies/ml
relationship between adverse events grade 3 or 4 related to PI and plasma concentration at week 2 (W2)
relationship between pharmacokinetic parameters and/or plasma concentrations and the drop of viral load between day 0 (D0) and W2 and between D0 and week 4 (W4)
relationship between pharmacokinetic parameters and viral mutations occurring during the treatment of patients with virological failure (over 1000 copies/ml after week 24 [W24])
PI pharmacokinetic parameter estimation and evaluation of variability
pharmacokinetic variability of nucleoside analogues at W2
intracellular concentration of nucleoside triphosphate derivatives at W2 (trough and maximum) and relationship between virological response and adverse events
relationship between inhibitory quotient of indinavir and virological response
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2005.
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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.
Dominique Salmon, MD principal investigator
Service de Medecine Interne Hopital Cochin Paris
France Mentre, MD study chair
Inserm EMI 03 57
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing nelfinavir, lopinavir/r and indinavir in people with HIV Infections, run by French National Agency for Research on AIDS and Viral Hepatitis at 1 site in France.
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 6 inclusion and 13 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 1 Aug 2005. 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 France. 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.
Are results available for this study?
The study was stopped early. 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?
treatment failure defined as viral load greater than 200 copies/ml between week 16 (W16) and week 48 (W48) (confirmed by 2 samples spiked at least 15 days apart but no more than 45 days after virological failure, assayed by 50 copies/ml method). The study lists 2 primary outcomes in all. 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 1 Aug 2005.