Clinical Trial Results:
A randomized, open, parallel design study to evaluate the effect on liver fat, adipose tissue and metabolic parameters when switching a protease inhibitor or efavirenz to once daily raltegravir in HIV-infected patients with body mass index over 25 kg/m2 and with at least one metabolic syndrome component.

Trial information Top of page
Trial identification
Sponsor protocol code	OBERAL
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Helsinki University Hospital Infectious Disease Clinic
Sponsor organisation address	Kolmiosairaala Haartmaninkatu 4, Helsinki, Finland, 00290
Public contact	Dr. Jussi Sutinen, Helsinki University Hospital, jussi.sutinen@hus.fi
Scientific contact	Dr. Jussi Sutinen, Helsinki University Hospital, 358 407480437, jussi.sutinen@hus.fi
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	30 Sep 2020
Is this the analysis of the primary completion data?	Yes
Primary completion date	02 Nov 2019
Global end of trial reached?	Yes
Global end of trial date	02 Nov 2019
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To evaluate the effect of switching from a protease inhibitor or efavirenz to raltegravir on liver fat content.
Protection of trial subjects	Subjects had direct phone numbers to the investigators and could contact them 24/7. Local anesthesia was used with invasive procedures.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	04 Dec 2017
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	Finland: 45
Worldwide total number of subjects	45
EEA total number of subjects	45
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)	43
From 65 to 84 years	2
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	All subjects were recruited from Finland during the period of Oct 2017 - April 2019.
Pre-assignment
Screening details	HIV-infected patients who were overweight or obese and had at least one metabolic syndrome component, or who had fatty liver diagnosed by imaging studies .
Pre-assignment period milestones
Number of subjects started	45
Number of subjects completed	45
Period 1
Period 1 title	Overall Trial (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Not blinded
Blinding implementation details	This is an open label randomized controlled study.
Arms
Are arms mutually exclusive	Yes
Arm title	Raltegravir
Arm description	Those subjects who switched their earlier protease inhibitor or efavirenz to raltegravir.
Arm type	Experimental
Investigational medicinal product name	raltegravir
Investigational medicinal product code	J05AJ01
Other name
Pharmaceutical forms	Film-coated tablet
Routes of administration	Oral use
Dosage and administration details	Raltegravir was taken 1200 mg once a day.
Arm title	Control
Arm description	Subjects who continued their protease inhibitor or efavirenz containing antiretroviral regimen unchanged.
Arm type	Active comparator
Investigational medicinal product name	efavirenz
Investigational medicinal product code	J05AG03
Other name
Pharmaceutical forms	Coated tablet
Routes of administration	Oral use
Dosage and administration details	The control subjects continued their efavirenz (600mg QD) or protease inhibitor containing regimen unchanged.
Number of subjects in period 1 Raltegravir Control Started 21 24 Completed 19 23 Not completed 2 1      Consent withdrawn by subject 2 -      Adverse event, non-fatal - 1

Subject disposition Top of page

Baseline characteristics Top of page

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Raltegravir
Reporting group description	Those subjects who switched their earlier protease inhibitor or efavirenz to raltegravir.
Reporting group title	Control
Reporting group description	Subjects who continued their protease inhibitor or efavirenz containing antiretroviral regimen unchanged.

End points Top of page

Primary: Change in liver fat content from baseline to 24 weeks. Top of page
End point title	Change in liver fat content from baseline to 24 weeks.
End point description
End point type	Primary
End point timeframe	The change in liver fat between baseline and 24 weeks.
End point values Raltegravir Control Number of subjects analysed 18 21 Units: liver fat fraction (%)     median (inter-quartile range (Q1-Q3)) 0.6 (-0.3 to 1.6) 0.3 (-0.5 to 2.7)
Statistical analysis title	Comparison
Statistical analysis description	The change from baseline and 24 weeks within the study groups and between the study groups were analyzed
Comparison groups	Raltegravir v Control
Number of subjects included in analysis	39
Analysis specification	Pre-specified
Analysis type	other [1]
P-value	> 0.05 [2]
Method	Wilcoxon (Mann-Whitney)
Parameter type	Median difference (net)
Confidence interval
Notes [1] - Within group changes were analyzed using Wilcoxon signed rank test and differences between the groups were analyzed Mann-Whitney test. [2] - non significant in all comparisons

Primary: Change in liver fat content from baseline to 24 weeks. Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	8 Feb 2018 - 2 Nov 2019.
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	20.0
Reporting groups
Reporting group title	Raltegravir
Reporting group description	-
Reporting group title	Control
Reporting group description	-
Serious adverse events Raltegravir Control Total subjects affected by serious adverse events      subjects affected / exposed 0 / 19 (0.00%) 1 / 24 (4.17%)      number of deaths (all causes) 0 0      number of deaths resulting from adverse events 0 Gastrointestinal disorders Pancreatitis      subjects affected / exposed 0 / 19 (0.00%) 1 / 24 (4.17%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events Raltegravir Control Total subjects affected by non serious adverse events      subjects affected / exposed 16 / 19 (84.21%) 20 / 24 (83.33%) Nervous system disorders dizzyness      subjects affected / exposed 5 / 19 (26.32%) 8 / 24 (33.33%)      occurrences all number 16 20 Headache      subjects affected / exposed 9 / 19 (47.37%) 8 / 24 (33.33%)      occurrences all number 16 20 Gastrointestinal disorders Nausea      subjects affected / exposed 9 / 19 (47.37%) 7 / 24 (29.17%)      occurrences all number 16 20

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? No
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

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