Ignite Creation Date:
2024-05-05 @ 12:08 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00256828
Status:
COMPLETED
Last Update Posted:
2007-10-16
First Post:
2005-11-21
Brief Title:
Once a Day QD - Twice a Day BID Clinical Trial Didanosine Lamivudine and Efavirenz Versus Zidovudine Lamivudine and Efavirenz in the Starting Treatment of HIV
Sponsor:
Clinical Trial Agency of HIV Study Group
Organization:
Clinical Trial Agency of HIV Study Group
Study Overview
Official Title:
A Multicenter Randomized Open Label Clinical Trial Comparing a QD Regimen of Didanosine Lamivudine and Efavirenz With a Standard BID Regimen of Zidovudine Lamivudine and Efavirenz in the Starting Treatment of Human Immunodeficiency Virus Infection GESIDA 3903
Status:
COMPLETED
Status Verified Date:
2005-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to compare the antiviral activity of two treatment groups for HIV chronic infection a QD regimen of didanosine lamivudine and efavirenz versus a BID regimen of zidovudine lamivudine and efavirenz Both will be administered with food in the starting treatment of human immunodeficiency virus infection at Week 48
Detailed Description:
The inhibition of HIV replication mediated by HAART causes an actual immunological reconstitution that has been clinically evidenced as a dramatic reduction in mortality incidence of opportunistic diseases hospital admissions and costs associated with healthcare in HIV-infected patients which has been shown since the year 1996 Unfortunately the eradication of HIV is not feasible with the therapies available therefore treatment of HIV infection is currently approached as a life-long strategy HAART is not free from middle and long-term adverse events
It must be considered that until relatively recently the HAART regimens required taking a high number of tablets several times daily frequently with diet restrictions which made compliance difficult and improved the quality of life of the patients In any case it must be noted that insufficient compliance with HAART can have harmful consequences for the patient public health and health resources
The factors predicting compliance with ART can depend on the patient the healthcare team and the therapeutic regimen
As mentioned above until recent dates HAART has gathered all factors making compliance difficult long-term duration over one drug over one dose daily and presence of adverse events Therefore the adequate compliance is an actual challenge for patients and for the health staff and has been considered with a good criterion the weak point of antiretroviral treatment
For all the above it can be stated that the ideal HAART regimen would be that with few tablets and that could be taken once daily The expected advantages of QD regimens could include mainly three first they will improve compliance which will have a highly positive effect on the antiviral efficacy of HAART On the other hand QD regimens will enable that HAART is better adapted to the lifestyle of the patient and will have a low interference with working hours so they will be more convenient and improve quality of life Finally it must be noted that QD regimens will enable for monitoring HAART directly and will allow for a relatively significant group of patients in our setting to follow the treatment with a greater guarantee of success such as those with problems of drug addiction lack of social support mental disease and those admitted to penitentiary centers
The main disadvantage of QD regimens is the virtual lack of large clinical trials comparing this therapeutic approach to other potent well-established BID regimens Therefore it is very interesting to examine this approach in a randomized clinical trial with an adequate design such as that proposed
The second problem is the consequences that result of missing a dose since this could entail that for some time - in the 24 hours following the failure - the drug concentrations could decrease enough to stop inhibiting viral replication this could also promote the emergence of viral strains resistant to the drugs In principle the implications of missing a dose depend substantially on the pharmacokinetic properties included in the QD regimen Cmin half-life intracellular concentrations and the IC50 of the HIV of each patient so that the higher the drug half-life and the higher the CminIC50 ratio the higher the probability that alter missing a dose the Cmin persists above the IC50 of the HIV strain of the patient Therefore it is important to select drugs with pharmacokinetic profiles and an antiviral potency enough for QD administration vide infra
BID regimen efavirenz zidovudine lamivudine
In this study we have chosen as BID regimen that containing NNRTI efavirenz Sustiva and Combivir which is the commercial combination of the NRTI zidovudine lamivudine that will lead patients to take one tablet in the morning and 2 tablets at night We have chosen this regimen zidovudine lamivudine efavirenz because it is the starting treatment regimen for HIV chronic infection best studied and considered by many as the gold standard for this indication
QD regimen efavirenz didanosine lamivudine
The QD regimen will be made up by didanosine capsule-CT lamivudine efavirenz a regimen containing three tablets that must be taken together at night and which is the QD regimen with most experience to date We have chosen as combination of NRTI didanosine and lamivudine drugs authorized for QD use with a very good safety profile and no interactions with each other and with efavirenz The combination of didanosine and lamivudine is highly attractive and is in fact recommended for the starting HAART by various agencies though not at the same level as the combination of zidovudine and lamivudine which can be only administered BID just because there are less randomized clinical trials with the former than with the latter combination of NRTI Therefore one of the strengths of the study is that it proposes the possibility of assessing the combination of didanosine and lamivudine in a starting HAART regimen
In this study the patients allocated to the QD regimen containing didanosine capsule-CT lamivudine efavirenz will take all tablets together at night with dinner In principle this involves a minor deviation from the data sheet of didanosine where it is specified that the drug must be taken fasting
Didanosine is the second antiretroviral drug marketed and in the last decade the presentation and dosage form of this drug have improved remarkably from bags with buffered powder for twice daily administration with dispersible tablets with buffer to the current dosage form which is a gastroresistant capsule capsule-CT which allows for administration in once daily doses and that since it has no buffer has improved substantially the gastric tolerance to the drug
The formulations of didanosine as powder or buffered dispersible tablets must be taken fasting for absorption to be optimum since its administration with food reduces significantly drug absorption and plasma concentrations However the effect of food on the absorption of capsules-CT does not cause an unequivocal reduction in drug exposure
Primary Objective
To compare the antiviral activity of the two treatment groups QD vs BID at Week 48 based on the percentage of patients with HIV-RNA levels 50 cml
Secondary Objectives
To compare the percentage of patients responding to the treatment with HIV-RNA levels 400 cml at Week 48 with the same approach of analysis as for the primary objective
To compare the time to therapy failure at Week 48 in both treatment regimens
To compare the increase in the CD4 cell levels from baseline to Week 48 in both treatment regiments
To compare the impact on the quality of life of both treatment regimens
To compare compliance of both treatment regimens
To compare the safety and tolerance of both treatment regimens along the 48 weeks of treatment
To assess the efficacy of the administration of didanosine together with food
Randomization Procedure
The randomization will be centralized and stratified by the baseline viral burden level being higher or lower than 100000 copml The patients giving their written informed consent will be included in the study To include a patient the clinical trial agency Gesida will be contacted by phone
Study Procedures
HIV-RNA CD4 and routine labs will be collected at screening baseline w1 w4 w12 w24 and w48 Quality of life will be measured with a self-patient report questionnaire MOS-HIV
It must be considered that until relatively recently the HAART regimens required taking a high number of tablets several times daily frequently with diet restrictions which made compliance difficult and improved the quality of life of the patients In any case it must be noted that insufficient compliance with HAART can have harmful consequences for the patient public health and health resources
The factors predicting compliance with ART can depend on the patient the healthcare team and the therapeutic regimen
As mentioned above until recent dates HAART has gathered all factors making compliance difficult long-term duration over one drug over one dose daily and presence of adverse events Therefore the adequate compliance is an actual challenge for patients and for the health staff and has been considered with a good criterion the weak point of antiretroviral treatment
For all the above it can be stated that the ideal HAART regimen would be that with few tablets and that could be taken once daily The expected advantages of QD regimens could include mainly three first they will improve compliance which will have a highly positive effect on the antiviral efficacy of HAART On the other hand QD regimens will enable that HAART is better adapted to the lifestyle of the patient and will have a low interference with working hours so they will be more convenient and improve quality of life Finally it must be noted that QD regimens will enable for monitoring HAART directly and will allow for a relatively significant group of patients in our setting to follow the treatment with a greater guarantee of success such as those with problems of drug addiction lack of social support mental disease and those admitted to penitentiary centers
The main disadvantage of QD regimens is the virtual lack of large clinical trials comparing this therapeutic approach to other potent well-established BID regimens Therefore it is very interesting to examine this approach in a randomized clinical trial with an adequate design such as that proposed
The second problem is the consequences that result of missing a dose since this could entail that for some time - in the 24 hours following the failure - the drug concentrations could decrease enough to stop inhibiting viral replication this could also promote the emergence of viral strains resistant to the drugs In principle the implications of missing a dose depend substantially on the pharmacokinetic properties included in the QD regimen Cmin half-life intracellular concentrations and the IC50 of the HIV of each patient so that the higher the drug half-life and the higher the CminIC50 ratio the higher the probability that alter missing a dose the Cmin persists above the IC50 of the HIV strain of the patient Therefore it is important to select drugs with pharmacokinetic profiles and an antiviral potency enough for QD administration vide infra
BID regimen efavirenz zidovudine lamivudine
In this study we have chosen as BID regimen that containing NNRTI efavirenz Sustiva and Combivir which is the commercial combination of the NRTI zidovudine lamivudine that will lead patients to take one tablet in the morning and 2 tablets at night We have chosen this regimen zidovudine lamivudine efavirenz because it is the starting treatment regimen for HIV chronic infection best studied and considered by many as the gold standard for this indication
QD regimen efavirenz didanosine lamivudine
The QD regimen will be made up by didanosine capsule-CT lamivudine efavirenz a regimen containing three tablets that must be taken together at night and which is the QD regimen with most experience to date We have chosen as combination of NRTI didanosine and lamivudine drugs authorized for QD use with a very good safety profile and no interactions with each other and with efavirenz The combination of didanosine and lamivudine is highly attractive and is in fact recommended for the starting HAART by various agencies though not at the same level as the combination of zidovudine and lamivudine which can be only administered BID just because there are less randomized clinical trials with the former than with the latter combination of NRTI Therefore one of the strengths of the study is that it proposes the possibility of assessing the combination of didanosine and lamivudine in a starting HAART regimen
In this study the patients allocated to the QD regimen containing didanosine capsule-CT lamivudine efavirenz will take all tablets together at night with dinner In principle this involves a minor deviation from the data sheet of didanosine where it is specified that the drug must be taken fasting
Didanosine is the second antiretroviral drug marketed and in the last decade the presentation and dosage form of this drug have improved remarkably from bags with buffered powder for twice daily administration with dispersible tablets with buffer to the current dosage form which is a gastroresistant capsule capsule-CT which allows for administration in once daily doses and that since it has no buffer has improved substantially the gastric tolerance to the drug
The formulations of didanosine as powder or buffered dispersible tablets must be taken fasting for absorption to be optimum since its administration with food reduces significantly drug absorption and plasma concentrations However the effect of food on the absorption of capsules-CT does not cause an unequivocal reduction in drug exposure
Primary Objective
To compare the antiviral activity of the two treatment groups QD vs BID at Week 48 based on the percentage of patients with HIV-RNA levels 50 cml
Secondary Objectives
To compare the percentage of patients responding to the treatment with HIV-RNA levels 400 cml at Week 48 with the same approach of analysis as for the primary objective
To compare the time to therapy failure at Week 48 in both treatment regimens
To compare the increase in the CD4 cell levels from baseline to Week 48 in both treatment regiments
To compare the impact on the quality of life of both treatment regimens
To compare compliance of both treatment regimens
To compare the safety and tolerance of both treatment regimens along the 48 weeks of treatment
To assess the efficacy of the administration of didanosine together with food
Randomization Procedure
The randomization will be centralized and stratified by the baseline viral burden level being higher or lower than 100000 copml The patients giving their written informed consent will be included in the study To include a patient the clinical trial agency Gesida will be contacted by phone
Study Procedures
HIV-RNA CD4 and routine labs will be collected at screening baseline w1 w4 w12 w24 and w48 Quality of life will be measured with a self-patient report questionnaire MOS-HIV
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None