Clinical Trial Results:
PILOT STUDY TO ASSESS THE ROLE OF IMMUNE ACTIVATION AND APOPTOSIS AS A MARKER FOR TREATMENT INTENSIFICATION WITH RALTEGRAVIR IN HIV-INFECTED PATIENTS ON ANTIRETROVIRAL THERAPY WITH LONG-TERM VIRAL SUPPRESSION AND UNFAVOURABLE IMMUNOLOGIC RESPONSE (DISCORDANT PATIENTS: V+I-).

Trial information Top of page
Trial identification
Sponsor protocol code	DISCOR-RAL
Additional study identifiers
ISRCTN number	-
US NCT number	NCT00773708
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Fundació Lluita contra la SIDA
Sponsor organisation address	Crta de Canyet s/n, Badalona, Spain, 08916
Public contact	CRA, Fundació Lluita contra la SIDA, +34 93 497 84 14, jtoro@flsida.org
Scientific contact	CRA, Fundació Lluita contra la SIDA, +34 93 497 84 14,
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	18 May 2011
Is this the analysis of the primary completion data?	Yes
Primary completion date	18 May 2011
Global end of trial reached?	Yes
Global end of trial date	18 May 2011
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To assess whether the intensification with Raltegravir affect the immune recovery in "discordant" patients with high level of CD8+HLADR+CD38+.
Protection of trial subjects	not specific
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	05 Mar 2009
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Spain: 44
Worldwide total number of subjects	44
EEA total number of subjects	44
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	44
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	We enrolled 49 HIV-1-infected subjects on suppressive HAART for at least 96 weeks.
Pre-assignment
Screening details	The final sample comprised 44 patients: 30 in the intensified arm and 14 in the control arm.
Period 1
Period 1 title	overall (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Not blinded
Arms
Are arms mutually exclusive	Yes
Arm title	Intensified arm (RAL arm)
Arm description	Intensification of previous therapy with Raltegravir
Arm type	Experimental
Investigational medicinal product name	raltegravir
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	400 mg/12h
Arm title	control arm
Arm description	Continue with the same antiretroviral therapy
Arm type	No intervention
Investigational medicinal product name	No investigational medicinal product assigned in this arm
Number of subjects in period 1 Intensified arm (RAL arm) control arm Started 30 14 Completed 25 14 Not completed 5 0      Consent withdrawn by subject 1 -      Adverse event, non-fatal 3 -      Protocol deviation 1 -

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Intensified arm (RAL arm)
Reporting group description	Intensification of previous therapy with Raltegravir
Reporting group title	control arm
Reporting group description	Continue with the same antiretroviral therapy
Reporting group values Intensified arm (RAL arm) control arm Total Number of subjects 30 14 44 Age categorical Units: Subjects     In utero 0 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0 0     Newborns (0-27 days) 0 0 0     Infants and toddlers (28 days-23 months) 0 0 0     Children (2-11 years) 0 0 0     Adolescents (12-17 years) 0 0 0     Adults (18-64 years) 30 14 44     From 65-84 years 0 0 0     85 years and over 0 0 0 Age continuous Units: years     median (inter-quartile range (Q1-Q3)) 48.5 (44 to 53.4) 45.5 (41.8 to 50.8) - Gender categorical Units: Subjects     Female 4 2 6     Male 26 12 38

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Intensified arm (RAL arm)
Reporting group description	Intensification of previous therapy with Raltegravir
Reporting group title	control arm
Reporting group description	Continue with the same antiretroviral therapy

End points Top of page

Primary: Impact of raltegravir intensification on CD4 T cell counts Top of page
End point title	Impact of raltegravir intensification on CD4 T cell counts
End point description
End point type	Primary
End point timeframe	from baseline to week 48
End point values Intensified arm (RAL arm) control arm Number of subjects analysed 30 14 Units: cells/mm3 median (inter-quartile range (Q1-Q3))     baseline 253 (208 to 301) 242 (188 to 292)     week 48 281 (230 to 320) 247 (212 to 411)
Statistical analysis title	Comparing medians between groups
Comparison groups	Intensified arm (RAL arm) v control arm
Number of subjects included in analysis	44
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.668
Method	Wilcoxon (Mann-Whitney)
Confidence interval

Primary: Impact of raltegravir intensification on CD4 T cell counts Top of page

Primary: Percentage CD4 T cell counts Top of page
End point title	Percentage CD4 T cell counts
End point description
End point type	Primary
End point timeframe	from baseline to week 48
End point values Intensified arm (RAL arm) control arm Number of subjects analysed 30 14 Units: cells/mm3 median (inter-quartile range (Q1-Q3))     baseline 19 (14 to 22) 19 (15 to 21)     week 48 19 (15 to 22) 18 (17 to 23)
Statistical analysis title	Comparing medians between groups
Comparison groups	Intensified arm (RAL arm) v control arm
Number of subjects included in analysis	44
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.761
Method	Wilcoxon (Mann-Whitney)
Confidence interval

Primary: Percentage CD4 T cell counts Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	from baseline to week 48
Assessment type	Non-systematic
Dictionary used for adverse event reporting
Dictionary name	DAIDS AE GRADING TAB
Dictionary version	1.0
Reporting groups
Reporting group title	Intensified arm (RAL arm)
Reporting group description	-
Serious adverse events Intensified arm (RAL arm) Total subjects affected by serious adverse events      subjects affected / exposed 2 / 30 (6.67%)      number of deaths (all causes) 0      number of deaths resulting from adverse events 0 Nervous system disorders Epilepsy      subjects affected / exposed 1 / 30 (3.33%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Gastrointestinal disorders Bowel obstruction      subjects affected / exposed 1 / 30 (3.33%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0
Frequency threshold for reporting non-serious adverse events: 1%
Non-serious adverse events Intensified arm (RAL arm) Total subjects affected by non serious adverse events      subjects affected / exposed 1 / 30 (3.33%) Gastrointestinal disorders Diarrhoea      subjects affected / exposed 1 / 30 (3.33%)      occurrences all number 1

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
29 Jan 2009	Protocol modified (wk 2 visit added + safety analysis added)
16 Apr 2009	Second phase added + information sheet form modified
29 May 2009	protocol modified (substudy included) and information sheet form modified
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

More information Top of page