Ignite Creation Date:
2024-05-06 @ 8:33 AM
Last Modification Date:
2024-10-26 @ 12:01 PM
Study NCT ID:
NCT02765776
Status:
COMPLETED
Last Update Posted:
2018-06-28
First Post:
2016-05-02
Brief Title:
An Observational Retrospective Database Analysis to Evaluate Raltegravir Based-regimens in Aged HIV Patients RalAge
Sponsor:
Azienda Policlinico Umberto I
Organization:
Azienda Policlinico Umberto I
Study Overview
Official Title:
An Observational Retrospective Database Analysis to Evaluate Raltegravir Based-regimens Including NUC-sparing Regimens in Aged HIV Patients RalAge
Status:
COMPLETED
Status Verified Date:
2016-05
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:
RalAge
Brief Summary:
RAL is considered one of the better-tolerated antiretroviral medications due to limited side effects and few long-term safety concerns Five-year clinical trial outcomes and clinical experience have demonstrated durable virologic suppression in both treatment-naïve and treatment-experienced patients including patients with extensive antiretroviral history and documented antiretroviral resistance Studies have also exhibited low adverse effect rates and reliable long-term safety lending to improved tolerance Several trials have evaluated the reduction in adverse effects in patients switched from various antiretroviral agents to RAL Treatment-naïve studies have demonstrated a lipid-neutral effect in patients on RAL-containing regimens When transitioning patients from a ritonavir-boosted PI regimen statistically significant decreases in total plasma cholesterol low-density lipoprotein and triglycerides were demonstrated Given its negligible interaction with the cytochrome P450 system RAL displays minimal drug-drug interactions making it a good option for ageing patients on multiple medications
This is an observational retrospective cohort in real world to describe RAL data including NUC-sparing regimens in aged HIV patients It is a phase IV study 90 patients will be enrolled from the Department of Public Health and Infectious Diseases of Sapienza University of Rome More than 4000 HIV patients are followed at this Department of Public Health and Infectious Diseases of Sapienza University of Rome More than 50 of these patients are 50 years From 10 to 12 are treated with a raltegravir based- regimen
The primary endpoint will be the description of the proportion of participants with an HIV-1 viral load 50 copiesmL
The secondary endpoints will be
Change from Baseline in CD4 T-cell counts CD8 cell counts CD4 CD8 ratio
Proportion of subjects with laboratory alterations
Proportion of patients with adverse events AE serious adverse events SAE also according to their severity
This is an observational retrospective cohort in real world to describe RAL data including NUC-sparing regimens in aged HIV patients It is a phase IV study 90 patients will be enrolled from the Department of Public Health and Infectious Diseases of Sapienza University of Rome More than 4000 HIV patients are followed at this Department of Public Health and Infectious Diseases of Sapienza University of Rome More than 50 of these patients are 50 years From 10 to 12 are treated with a raltegravir based- regimen
The primary endpoint will be the description of the proportion of participants with an HIV-1 viral load 50 copiesmL
The secondary endpoints will be
Change from Baseline in CD4 T-cell counts CD8 cell counts CD4 CD8 ratio
Proportion of subjects with laboratory alterations
Proportion of patients with adverse events AE serious adverse events SAE also according to their severity
Detailed Description:
Objectives The primary endpoint will be the description of the proportion of participants with an HIV-1 viral load 50 copiesmL
The secondary endpoints will be
Change from Baseline in CD4 T-cell counts CD8 cell counts CD4 CD8 ratio
Proportion of subjects with laboratory alterations
Proportion of patients with adverse events AE serious adverse events SAE also according to their severity
Hypotheses Being this a retrospective study a formal hypothesis is not formulated Background and Rationale Antiretroviral therapy has changed the natural history of HIV infection However antiretroviral therapy must be maintained for life Its potential long-term adverse effects may interact synergistically with the ageing process resulting in a higher incidence of comorbidities The increasing number of non-antiretroviral drugs used to treat comorbidities may also place the patient at a higher risk of clinically meaningful interactions Nowadays efficacy is well demonstrated by all antiretroviral drugs compared with previous times In fact a substantial number of HIV-infected patients from areas where antiretroviral therapy is widely available have achieved sustained suppression of plasma HIV replication In contrast the contributions of antiretroviral therapy to the development and progression of comorbidities and to the risk of potentially severe interactions have gained increasing importance as HIV-infected patients are getting older More than half of HIV-infected patients aged 50 years have been reported to suffer from two or more concomitant comorbidities In some of these patients maintenance of antiretroviral therapy with combinations including NRTIs or PIs may be challenging Data on ageing HIV patients under antiretroviral therapy are lacking
RAL is considered one of the better-tolerated antiretroviral medications due to limited side effects and few long-term safety concerns Five-year clinical trial outcomes and clinical experience have demonstrated durable virologic suppression in both treatment-naïve and treatment-experienced patients including patients with extensive antiretroviral history and documented antiretroviral resistance Studies have also exhibited low adverse effect rates and reliable long-term safety lending to improved tolerance Several trials have evaluated the reduction in adverse effects in patients switched from various antiretroviral agents to RAL Treatment-naïve studies have demonstrated a lipid-neutral effect in patients on RAL-containing regimens When transitioning patients from a ritonavir-boosted PI regimen statistically significant decreases in total plasma cholesterol low-density lipoprotein and triglycerides were demonstrated Given its negligible interaction with the cytochrome P450 system RAL displays minimal drug-drug interactions making it a good option for ageing patients on multiple medications
Study Design This is an observational retrospective cohort in real world to describe RAL data including NUC-sparing regimens in aged HIV patients It is a phase IV study 90 patients will be enrolled from the Department of Public Health and Infectious Diseases of Sapienza University of Rome More than 4000 HIV patients are followed at this Department of Public Health and Infectious Diseases of Sapienza University of Rome More than 50 of these patients are 50 years From 10 to 12 are treated with a raltegravir based- regimen
In this retrospective analysis all naïve patients on raltegravir-based regimens and all patients switched to raltegravir-based regimens will be considered For raltegravir-based regimens the investigators mean raltegravir as third agent in a triple regimen with NRTIs and also raltegravir-based regimens in NUC-sparing therapies
Raltegravir initiation is equivalent to baseline
All consecutive patients fulfilling the following inclusion criteria are considered eligible
HIV-1 infected patients
aged 60 years old
naive patients receiving raltegravir based-regimen including Nuc-sparing regimens
experienced patients with virological suppression HIV-1 RNA50 copies who had switched from any antiretroviral drug to raltegravir-based regimens including Nuc-sparing regimens because of toxicity convenience or other reasons
Data are collected from medical records The Time horizon for patient follow-up for outcome is at least 12 months
The following information will be extracted from the database of the Department
demographics age sex race
smoking
risk factors for HIV infection
time from HIV-1 diagnosis years
history of AIDS diagnosis
hepatitis C virus HCV co-infection
hepatitis B virus HBV co-infection
presence of co-morbidities including diabetes hypertension CVD CKD cancer etc
reasons for switching to raltegravir
time with HIV-1 RNA 50 copiesmL before switch
BMI
Hematology Hb PLT
Creatinine
eGFR CKD-EPI formula
Phosphorus
Calcium
AST
ALT
alkaline phosphatase
total direct indirect bilirubin
proteinuria
total HDL- LDL-cholesterol
triglycerides
glycemia
HIV-RNA
CD4 CD8 CD4CD8 ratio since the start of raltegravir
previous ART regimen and number of previous antiretroviral agents
Follow-up will count from the date of start of raltegravir to VFTF or last available visit whichever first occurred
AEs were classified as mildmoderate severe or life threatening according to DAIDS Classification AEs were considered unrelated to RAL possibly related or related according to physician criteria
Safety data will be descriptive no comparison data will be analyzed
Study Procedures At study visits clinical data are collected and laboratory analyses comprising CD4 T cell count plasma HIV-1 RNA blood cells and plasma chemistry profiles including fasting lipids total cholesterol high-density lipoprotein cholesterol HDL low- density lipoprotein LDL cholesterol triglycerides are recorded Plasma HIV-1 RNA and all other laboratory determinations are performed locally at each site throughout the follow-up period
Study Duration The Time horizon for patient follow-up for outcome is at least 12 months
Statistical Analysis and Sample Size Justification Descriptive analyses
Baseline characteristics of enrolled patients will be presented as mean values standard deviation SD and median value with interquartile range absolute frequency relative frequency according to the variable type and distribution
Primary analysis The proportion of patients with an HIV-1 viral load 50 copiesmL will be expressed as frequency and percentage The 95 confidence intervals CIs of proportion and corresponding incidence rate will be calculated
Secondary analyses The change from baseline of continuous variables will be assessed by the Students t-test for paired data for normally distributed variables based on the Shapiro-Wilk statistics and the Wilcoxon signed-rank test for non normally distributes ones All tests will be two-sided and a p-value of less than 005 will be considered as statistically significant
Safety data analysis will be descriptive only Safety data AEs SAEs and laboratory alterations will be tabulated according to their severity for a descriptive purpose only
PowerSample Size
A sample size of 90 subjects produces two-sided 95 CI with the following width when the sample proportion of patients with an HIV-1 viral load 50 copiesmL is between 40 and 60 the 95 CI width is 02 that correspond to the possible maximum width in this study Corresponding widths are 017 for a sample proportion of 030 or 070 015 for a sample proportion of 020 or 080 and 013 for a sample proportion of 010 or 090 PASS 11 NCSS LLC Kaysville Utah USA
Specific Drug Supply Requirements No drug supply is required
Adverse Experience Reporting Safety data will be descriptive no comparison data will be analyzed If adverse events will be identified they will be reported to the Italian agency for Drugs AIFA according to the law
Safety Assessments For the International Conference on Harmonization ICH an AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment An AE can therefore be any unfavorable and unintended sign including an abnormal laboratory finding for example symptom or disease temporally associated with the use of a medicinal product whether or not considered related to this medicinal product
SAE is any untoward medical occurrence or effect that at any dose
1 Results in death
2 Is life-threatening
3 Requires hospitalization or prolongation of existing inpatients hospitalization
4 Results in persistent or significant disability or incapacity andor
5 Is a congenital anomaly or birth defect
6 Is a cancer
7 Is associated with an overdose
8 Is an Other Important Medical Event
Life-threatening in the definition of a serious adverse event refers to an event in which the subject was at risk of death at the time of event it does not refer to an event which hypothetically might have caused death if it were more severe
Medical judgment should be exercised in deciding whether an adverse eventreaction is serious in other situations Important adverse events reactions that are not immediately life-threatening or do not result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes listed in the definition above should also be considered serious
The severity of AEs will be graded according to the following definitions
Mild awareness of sign symptom or event but easily tolerated Moderate discomfort enough to cause interference with usual activity and may warrant intervention Severe incapacitating with inability to do normal daily living activities or significantly affects clinical status and warrants intervention Further details will be included in the study agreement
Publication Plan
The publication plan will consider one manuscript
The secondary endpoints will be
Change from Baseline in CD4 T-cell counts CD8 cell counts CD4 CD8 ratio
Proportion of subjects with laboratory alterations
Proportion of patients with adverse events AE serious adverse events SAE also according to their severity
Hypotheses Being this a retrospective study a formal hypothesis is not formulated Background and Rationale Antiretroviral therapy has changed the natural history of HIV infection However antiretroviral therapy must be maintained for life Its potential long-term adverse effects may interact synergistically with the ageing process resulting in a higher incidence of comorbidities The increasing number of non-antiretroviral drugs used to treat comorbidities may also place the patient at a higher risk of clinically meaningful interactions Nowadays efficacy is well demonstrated by all antiretroviral drugs compared with previous times In fact a substantial number of HIV-infected patients from areas where antiretroviral therapy is widely available have achieved sustained suppression of plasma HIV replication In contrast the contributions of antiretroviral therapy to the development and progression of comorbidities and to the risk of potentially severe interactions have gained increasing importance as HIV-infected patients are getting older More than half of HIV-infected patients aged 50 years have been reported to suffer from two or more concomitant comorbidities In some of these patients maintenance of antiretroviral therapy with combinations including NRTIs or PIs may be challenging Data on ageing HIV patients under antiretroviral therapy are lacking
RAL is considered one of the better-tolerated antiretroviral medications due to limited side effects and few long-term safety concerns Five-year clinical trial outcomes and clinical experience have demonstrated durable virologic suppression in both treatment-naïve and treatment-experienced patients including patients with extensive antiretroviral history and documented antiretroviral resistance Studies have also exhibited low adverse effect rates and reliable long-term safety lending to improved tolerance Several trials have evaluated the reduction in adverse effects in patients switched from various antiretroviral agents to RAL Treatment-naïve studies have demonstrated a lipid-neutral effect in patients on RAL-containing regimens When transitioning patients from a ritonavir-boosted PI regimen statistically significant decreases in total plasma cholesterol low-density lipoprotein and triglycerides were demonstrated Given its negligible interaction with the cytochrome P450 system RAL displays minimal drug-drug interactions making it a good option for ageing patients on multiple medications
Study Design This is an observational retrospective cohort in real world to describe RAL data including NUC-sparing regimens in aged HIV patients It is a phase IV study 90 patients will be enrolled from the Department of Public Health and Infectious Diseases of Sapienza University of Rome More than 4000 HIV patients are followed at this Department of Public Health and Infectious Diseases of Sapienza University of Rome More than 50 of these patients are 50 years From 10 to 12 are treated with a raltegravir based- regimen
In this retrospective analysis all naïve patients on raltegravir-based regimens and all patients switched to raltegravir-based regimens will be considered For raltegravir-based regimens the investigators mean raltegravir as third agent in a triple regimen with NRTIs and also raltegravir-based regimens in NUC-sparing therapies
Raltegravir initiation is equivalent to baseline
All consecutive patients fulfilling the following inclusion criteria are considered eligible
HIV-1 infected patients
aged 60 years old
naive patients receiving raltegravir based-regimen including Nuc-sparing regimens
experienced patients with virological suppression HIV-1 RNA50 copies who had switched from any antiretroviral drug to raltegravir-based regimens including Nuc-sparing regimens because of toxicity convenience or other reasons
Data are collected from medical records The Time horizon for patient follow-up for outcome is at least 12 months
The following information will be extracted from the database of the Department
demographics age sex race
smoking
risk factors for HIV infection
time from HIV-1 diagnosis years
history of AIDS diagnosis
hepatitis C virus HCV co-infection
hepatitis B virus HBV co-infection
presence of co-morbidities including diabetes hypertension CVD CKD cancer etc
reasons for switching to raltegravir
time with HIV-1 RNA 50 copiesmL before switch
BMI
Hematology Hb PLT
Creatinine
eGFR CKD-EPI formula
Phosphorus
Calcium
AST
ALT
alkaline phosphatase
total direct indirect bilirubin
proteinuria
total HDL- LDL-cholesterol
triglycerides
glycemia
HIV-RNA
CD4 CD8 CD4CD8 ratio since the start of raltegravir
previous ART regimen and number of previous antiretroviral agents
Follow-up will count from the date of start of raltegravir to VFTF or last available visit whichever first occurred
AEs were classified as mildmoderate severe or life threatening according to DAIDS Classification AEs were considered unrelated to RAL possibly related or related according to physician criteria
Safety data will be descriptive no comparison data will be analyzed
Study Procedures At study visits clinical data are collected and laboratory analyses comprising CD4 T cell count plasma HIV-1 RNA blood cells and plasma chemistry profiles including fasting lipids total cholesterol high-density lipoprotein cholesterol HDL low- density lipoprotein LDL cholesterol triglycerides are recorded Plasma HIV-1 RNA and all other laboratory determinations are performed locally at each site throughout the follow-up period
Study Duration The Time horizon for patient follow-up for outcome is at least 12 months
Statistical Analysis and Sample Size Justification Descriptive analyses
Baseline characteristics of enrolled patients will be presented as mean values standard deviation SD and median value with interquartile range absolute frequency relative frequency according to the variable type and distribution
Primary analysis The proportion of patients with an HIV-1 viral load 50 copiesmL will be expressed as frequency and percentage The 95 confidence intervals CIs of proportion and corresponding incidence rate will be calculated
Secondary analyses The change from baseline of continuous variables will be assessed by the Students t-test for paired data for normally distributed variables based on the Shapiro-Wilk statistics and the Wilcoxon signed-rank test for non normally distributes ones All tests will be two-sided and a p-value of less than 005 will be considered as statistically significant
Safety data analysis will be descriptive only Safety data AEs SAEs and laboratory alterations will be tabulated according to their severity for a descriptive purpose only
PowerSample Size
A sample size of 90 subjects produces two-sided 95 CI with the following width when the sample proportion of patients with an HIV-1 viral load 50 copiesmL is between 40 and 60 the 95 CI width is 02 that correspond to the possible maximum width in this study Corresponding widths are 017 for a sample proportion of 030 or 070 015 for a sample proportion of 020 or 080 and 013 for a sample proportion of 010 or 090 PASS 11 NCSS LLC Kaysville Utah USA
Specific Drug Supply Requirements No drug supply is required
Adverse Experience Reporting Safety data will be descriptive no comparison data will be analyzed If adverse events will be identified they will be reported to the Italian agency for Drugs AIFA according to the law
Safety Assessments For the International Conference on Harmonization ICH an AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment An AE can therefore be any unfavorable and unintended sign including an abnormal laboratory finding for example symptom or disease temporally associated with the use of a medicinal product whether or not considered related to this medicinal product
SAE is any untoward medical occurrence or effect that at any dose
1 Results in death
2 Is life-threatening
3 Requires hospitalization or prolongation of existing inpatients hospitalization
4 Results in persistent or significant disability or incapacity andor
5 Is a congenital anomaly or birth defect
6 Is a cancer
7 Is associated with an overdose
8 Is an Other Important Medical Event
Life-threatening in the definition of a serious adverse event refers to an event in which the subject was at risk of death at the time of event it does not refer to an event which hypothetically might have caused death if it were more severe
Medical judgment should be exercised in deciding whether an adverse eventreaction is serious in other situations Important adverse events reactions that are not immediately life-threatening or do not result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes listed in the definition above should also be considered serious
The severity of AEs will be graded according to the following definitions
Mild awareness of sign symptom or event but easily tolerated Moderate discomfort enough to cause interference with usual activity and may warrant intervention Severe incapacitating with inability to do normal daily living activities or significantly affects clinical status and warrants intervention Further details will be included in the study agreement
Publication Plan
The publication plan will consider one manuscript
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