Trial Outcomes & Findings for Effects of Raltegravir Based Regimen on Platelet Reactivity, Platelet-monocyte Aggregation and Immune Activation (NCT NCT02383355)

Results Overview

Platelet expression of the platelet activation marker CD62P (P-selectin) and of the activated fibrinogen receptor (αIIbβ3) through fibrinogen binding following stimulation with two concentrations of the platelet agonists ADP (adenosine diphosphate) and CRP-XL (crosslinked collagen related peptide). Difference between week 0 and week 10. Primary outcome is CD62p expression upon stimulation with ADP (power calculation based on this measure). Expression of both markers are expressed as MFI (Median fluorescence intensity) and measured by flowcytometry. Change after 10 weeks was calculated as a ratio between baseline and week 10.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

40 participants

Primary outcome timeframe

Baseline and week 10

Results posted on

2019-01-10

Participant Flow

Participant milestones

Participant milestones
Measure	Switch Group Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy for 10 weeks Raltegravir: Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy	Continuation Group Individuals in the continuation group will continue the regimen, which consists of antiretroviral therapy as indicated in the inclusion criteria Continuation of own regimen: Continuation of own antiretroviral medication during the 10 weeks follow-up
Overall Study STARTED	19	21
Overall Study COMPLETED	17	21
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Switch Group Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy for 10 weeks Raltegravir: Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy	Continuation Group Individuals in the continuation group will continue the regimen, which consists of antiretroviral therapy as indicated in the inclusion criteria Continuation of own regimen: Continuation of own antiretroviral medication during the 10 weeks follow-up
Overall Study Adverse Event	2	0

Baseline Characteristics

Effects of Raltegravir Based Regimen on Platelet Reactivity, Platelet-monocyte Aggregation and Immune Activation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Switch Group n=19 Participants Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy for 10 weeks Raltegravir: Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy	Continuation Group n=21 Participants Individuals in the continuation group will continue the regimen, which consists of antiretroviral therapy as indicated in the inclusion criteria Continuation of own regimen: Continuation of own antiretroviral medication during the 10 weeks follow-up	Total n=40 Participants Total of all reporting groups
Age, Continuous	48 years n=5 Participants	49 years n=7 Participants	48 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	21 Participants n=7 Participants	39 Participants n=5 Participants
Region of Enrollment Netherlands	19 participants n=5 Participants	21 participants n=7 Participants	40 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and week 10

Population: Intention to treat, if week 10 is not available, week 4 was used for these individuals (n=2)

Platelet expression of the platelet activation marker CD62P (P-selectin) and of the activated fibrinogen receptor (αIIbβ3) through fibrinogen binding following stimulation with two concentrations of the platelet agonists ADP (adenosine diphosphate) and CRP-XL (crosslinked collagen related peptide). Difference between week 0 and week 10. Primary outcome is CD62p expression upon stimulation with ADP (power calculation based on this measure). Expression of both markers are expressed as MFI (Median fluorescence intensity) and measured by flowcytometry. Change after 10 weeks was calculated as a ratio between baseline and week 10.

Outcome measures

Outcome measures
Measure	Switch Group n=19 Participants Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy for 10 weeks Raltegravir: Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy	Continuation Group n=21 Participants Individuals in the continuation group will continue the regimen, which consists of antiretroviral therapy as indicated in the inclusion criteria Continuation of own regimen: Continuation of own antiretroviral medication during the 10 weeks follow-up
Platelet Reactivity Measured by Expression of P-selectin (CD62p) and Fibrinogen Binding ADP 125uM CD62p expression	0.9 Ratio Interval 0.49 to 1.14	0.96 Ratio Interval 0.66 to 1.3
Platelet Reactivity Measured by Expression of P-selectin (CD62p) and Fibrinogen Binding ADP 125uM Fibrinogen binding	1 Ratio Interval 0.37 to 2.8	0.99 Ratio Interval 0.66 to 1.95
Platelet Reactivity Measured by Expression of P-selectin (CD62p) and Fibrinogen Binding ADP 7.8uM CD62p expression	0.88 Ratio Interval 0.46 to 1.11	0.99 Ratio Interval 0.69 to 1.32
Platelet Reactivity Measured by Expression of P-selectin (CD62p) and Fibrinogen Binding ADP 7.8uM fibrinogen binding	0.85 Ratio Interval 0.39 to 2.13	1.02 Ratio Interval 0.57 to 1.53
Platelet Reactivity Measured by Expression of P-selectin (CD62p) and Fibrinogen Binding CRP (collagen) XL 655ng/ml CD62p expression	0.95 Ratio Interval 0.87 to 1.2	0.94 Ratio Interval 0.68 to 1.28
Platelet Reactivity Measured by Expression of P-selectin (CD62p) and Fibrinogen Binding CRP (collagen) XL 655ng/ml fibrinogen binding	0.8 Ratio Interval 0.48 to 1.77	0.8 Ratio Interval 0.64 to 1.38
Platelet Reactivity Measured by Expression of P-selectin (CD62p) and Fibrinogen Binding CRP (collagen) XL 27.33ng/ml CD62p expression	0.87 Ratio Interval 0.41 to 2.14	0.84 Ratio Interval 0.33 to 1.84
Platelet Reactivity Measured by Expression of P-selectin (CD62p) and Fibrinogen Binding CRP (collagen) XL 27.33 ng/ml fibrinogen binding	0.88 Ratio Interval 0.68 to 1.59	1.04 Ratio Interval 0.41 to 1.59

SECONDARY outcome

Timeframe: Baseline and week 10

Platelet monocyte complex (PMCs) measured by flow-cytometry. % of CD61+ (platelet-marker) monocytes. Change after 10 weeks was calculated as a ratio between baseline and week 10.

Outcome measures

Outcome measures
Measure	Switch Group n=19 Participants Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy for 10 weeks Raltegravir: Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy	Continuation Group n=21 Participants Individuals in the continuation group will continue the regimen, which consists of antiretroviral therapy as indicated in the inclusion criteria Continuation of own regimen: Continuation of own antiretroviral medication during the 10 weeks follow-up
Platelet-leukocyte Aggregates (Platelet Monocyte Complex Measured by Flow-cytometry)	0.95 ratio Interval 0.113 to 4.087	0.932 ratio Interval 0.198 to 3.604

SECONDARY outcome

Timeframe: Baseline and Week 10

Markers of persistent immune activation measured by flow cytometry (% of CD4-cells positive for CD38HLA-DR cells). Change after 10 weeks was calculated as a ratio between baseline and week 10.

Outcome measures

Outcome measures
Measure	Switch Group n=19 Participants Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy for 10 weeks Raltegravir: Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy	Continuation Group n=21 Participants Individuals in the continuation group will continue the regimen, which consists of antiretroviral therapy as indicated in the inclusion criteria Continuation of own regimen: Continuation of own antiretroviral medication during the 10 weeks follow-up
T-cell Dysfunction (CD4-cells)	1.314 ratio Interval 0.309 to 10.78	1.016 ratio Interval 0.023 to 3.347

SECONDARY outcome

Timeframe: Baseline and week 10

Plasma levels of hs-CRP (ng/mL) measured by ELISA . Change in concentration was calculated as a ratio between baseline (week 0) and week 10.

Outcome measures

Outcome measures
Measure	Switch Group n=19 Participants Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy for 10 weeks Raltegravir: Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy	Continuation Group n=18 Participants Individuals in the continuation group will continue the regimen, which consists of antiretroviral therapy as indicated in the inclusion criteria Continuation of own regimen: Continuation of own antiretroviral medication during the 10 weeks follow-up
Circulating Levels of High Sensitive C-reactive Protein (Hs-CRP)	1.208 ratio Standard Deviation 0.895	1.103 ratio Standard Deviation 1.007

SECONDARY outcome

Timeframe: Baseline and week 10

Monocyte subsets measured by flowcytometry. Classical monocytes (CD14+,CD16-), intermediate (CD14+CD16+), Non-classical (CD14dimCD16+). Reported values are change between baseline and week 10 and reported as ratio.

Outcome measures

Outcome measures
Measure	Switch Group n=19 Participants Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy for 10 weeks Raltegravir: Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy	Continuation Group n=21 Participants Individuals in the continuation group will continue the regimen, which consists of antiretroviral therapy as indicated in the inclusion criteria Continuation of own regimen: Continuation of own antiretroviral medication during the 10 weeks follow-up
Persistent Immune Activation - Monocyte Subsets classical monocytes as % of total monocytes	0.98 ratio Interval 0.777 to 1.095	0.998 ratio Interval 0.807 to 1.171
Persistent Immune Activation - Monocyte Subsets intermediate monocytes as % of total monocytes	1.042 ratio Interval 0.325 to 2.923	0.979 ratio Interval 0.448 to 2.509
Persistent Immune Activation - Monocyte Subsets non-classical monocytes as % of total monocytes	1 ratio Interval 0.567 to 2.128	1.089 ratio Interval 0.308 to 2.886

Adverse Events

Switch Group

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Continuation Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Switch Group n=19 participants at risk Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy for 10 weeks Raltegravir: Raltegravir 400mg tablets administered twice daily together with continuation of their own backbone therapy	Continuation Group n=21 participants at risk Individuals in the continuation group will continue the regimen, which consists of antiretroviral therapy as indicated in the inclusion criteria Continuation of own regimen: Continuation of own antiretroviral medication during the 10 weeks follow-up
Nervous system disorders headache	5.3% 1/19 • Number of events 1	0.00% 0/21
Nervous system disorders insomnia	5.3% 1/19 • Number of events 1	0.00% 0/21

Additional Information

Wouter van der Heijden

Radboudumc

Phone: 0031 24 3616980

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place