Antiphospholipid Syndrome (APS)Phase 2APLAQUINENCT02595346
Study of the Efficiency of Hydroxychloroquine on the Endothelial Dysfunction and Its Vascular Consequences During the Antiphospholipid Syndrome
A Phase 2 study testing Hydroxychloroquine in people with Antiphospholipid Syndrome (APS), run by University Hospital, Rouen at 1 site in France.
Trial summary
This study evaluates the benefits of hydroxychloroquine on arterial function in antiphospholipid syndrome. Briefly, the patients will be randomized in two groups, one will receive hydroxychloroquine and standard treatment, the other will receive placebo in addition of standard treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Antiphospholipid Syndrome (APS)
- What is being tested?
- Hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteFrance
- Study dates
- 17 May 2016to 5 Aug 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who fulfilled Sidney criteria for APS (antiphospholipid Syndrome
- Women of childbearing potential must have a contraceptive method
- Written informed consent
- no severe, progressive, or uncontrolled kidney, liver, blood, stomach, lung, heart, or brain disease.
Who cannot join
- secondary antiphospholipid syndrome
- Pregnancy and breastfeeding
- Patients with a history of severe depression, psychosis, or suicidal ideation
- story of intolerance or contra-indication to hydroxychloroquine, lactose, trinitrin
- Prior use of hydroxychloroquine in the last 6 months
- Chronic heart failure
Show all 14Show fewer
- atrial fibrillation
- severe pulmonary hypertension
- severe kidney failure clearance < 30ml/mn
- uncontrolled arterial hypertension
- secondary arterial hypertension
- diabetes mellitus diagnosed in the last 3 months
- body mass index > 35
- Patient has been committed to an institution by legal or regulatory order
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficiency of Hydroxychloroquine on the Endothelial Dysfunction in Antiphospholipid Syndrome (APLAQUINE)
This study evaluates the benefits of hydroxychloroquine on arterial function in antiphospholipid syndrome.
Briefly, the patients will be randomized in two groups, one will receive hydroxychloroquine and standard treatment, the other will receive placebo in addition of standard treatment.
Read the detailed description
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent thrombotic events and miscarriages, with persistently positive antiphospholipid antibodies (aPL). APS may be isolated (primary APS) or associated to a connective tissue disease, most often systemic lupus erythematous (SLE).
Pathogenic effects of aPL were first described by the demonstration that in vitro incubation of endothelial cells or monocytes with aPL induce an endothelial dysfunction characterized by pro-coagulant (overexpression of tissue factor and modulation of protein C and S), pro-inflammatory (increased level of IL-6(interleukin 6) , IL-1β and TNFα) and pro-adhesive (increased levels of ICAM-1(intercellular adhesion molecule ), VCAM-1 (vascular endothelial cell adhesion molecule) and E-selectin) phenotypes. In parallel the investigators and others reported that endothelial function, assessed by flow mediated dilatation, is altered in patients with primary and secondary forms of APS. Although a role for TLR (toll-like receptor )-mediated NFkB translocation has been advanced, the pathogenic mechanisms that lead to in vivo endothelial injury in APS are incompletely understood.
In an experimental model, the investigators demonstrated that passive transfer of human aPL to mice induced a marked endothelial dysfunction assessed ex vivo in small resistance arteries, and an increase in TNFα levels. Moreover, the investigators group have demonstrated that patients with primary arterial APS display endothelial dysfunction and structural arterial changes, associated with a pro-oxidative and pro-coagulant state and with activation of the TLR2 and TLR4 signalling pathways.
Recently, in a preliminary study the investigators have found that endothelial glycocalyx which is an important part of the vascular barrier and which is intimately linked to the homeostatic functions of the endothelium was altered in APL patients.
Hydroxychloroquine (HCQ) is an antimalarial drug, also used to treat rheumatic diseases such as SLE. There is experimental evidence to suggest a direct role of hydroxychloroquine on the pathophysiology of APS: it directly reduces the binding of antibodies on the phospholipid bilayers, protects the annexin A5 anticoagulant shield and it reverses platelet adhesion induced by aPL.
Furthermore it is known to decrease the expression of lysosomal TLRs, but also extra lysosomal TLR2 and TLR4.
The aim of this study is to investigate whether treatment with hydroxychloroquine modulates vascular endothelial function in patients.
- Conditions
- Antiphospholipid Syndrome (APS)
- Being tested
- Hydroxychloroquine, placebo
- Medical subject headings
- Antiphospholipid Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called plaquenil
endothelial function is assessed by measuring the flow mediated dilatation of humeral artery in response to ischemia. the dilatation is evaluated by echotracking.
glycocalyx thickness is measured by the study of sublingual microcirculation with SDF imaging.
oxydative, inflammatory and coagulation parameters is assessed on plasma samples.
placeboDrug
endothelial function is assessed by measuring the flow mediated dilatation of humeral artery in response to ischemia. the dilatation is evaluated by echotracking.
glycocalyx thickness is measured by the study of sublingual microcirculation with SDF imaging.
oxydative, inflammatory and coagulation parameters is assessed on plasma samples.
| Study group | Role | What they receive |
|---|---|---|
| hydroxychlorquine | Experimental | hydroxychloroquine 200 mg twice a day for 6 months Receives: Drug: Hydroxychloroquine |
| control | Placebo comparator | placebo 2 pills a day for 6 months Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline flow mediated dilatation of brachial artery
The brachial artery diameter and blood flow are measured by echotracking and Doppler before and just after and ischemic test. Result expressed in percentage of diameter variation.
Measured: 6 months
Secondary outcomes (5)
change from baseline in endothelial glycocalyx thickness
indirect measure of the glycocalyx thickness by using sublingual SDF (sidestream dark field) imaging
Measured: 6 months
change from baseline in oxydative stress
plasma levels of nitrites and TBARS (thiobarbituric acid reactive substance)
Measured: 6 months
change from baseline in systemic inflammation
plasma levels of TNFalpha
Measured: 6 months
change from baseline in coagulation parameter
Tissue factor plasmatic level
Measured: 6 months
change from baseline in plasmatic level in hydroxychloroquine
plasma level of hydroxychloroquine
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2015 (estimated)
- Study start17 May 2016
- Primary completion5 Aug 2020
- Study completion5 Aug 2020
Why it stopped: Difficulty in enrolling new patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Antiphospholipid Syndrome (APS)Studies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sébastien MIRANDA, MD, Principal investigator, University Hospital, Rouen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02595346
- Sponsor's protocol ID
- 2015/074/HP
- Acronym
- APLAQUINE
- Status last verified
- Apr 2026
- First submitted
- 2 Nov 2015
- Last updated
- 14 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficiency of Hydroxychloroquine on the Endothelial Dysfunction in Antiphospholipid Syndrome (APLAQUINE)
- ClinicalTrials.gov ID
- NCT02595346
- Acronym / sponsor ID
- APLAQUINE / 2015/074/HP
- Conditions
- Antiphospholipid Syndrome (APS)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty in enrolling new patients
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- 17 May 2016 (actual)
- Primary completion
- 5 Aug 2020 (actual)
- Study completion
- 5 Aug 2020 (actual)
- First posted
- 3 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the benefits of hydroxychloroquine on arterial function in antiphospholipid syndrome.
Briefly, the patients will be randomized in two groups, one will receive hydroxychloroquine and standard treatment, the other will receive placebo in addition of standard treatment.
Detailed description
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent thrombotic events and miscarriages, with persistently positive antiphospholipid antibodies (aPL). APS may be isolated (primary APS) or associated to a connective tissue disease, most often systemic lupus erythematous (SLE).
Pathogenic effects of aPL were first described by the demonstration that in vitro incubation of endothelial cells or monocytes with aPL induce an endothelial dysfunction characterized by pro-coagulant (overexpression of tissue factor and modulation of protein C and S), pro-inflammatory (increased level of IL-6(interleukin 6) , IL-1β and TNFα) and pro-adhesive (increased levels of ICAM-1(intercellular adhesion molecule ), VCAM-1 (vascular endothelial cell adhesion molecule) and E-selectin) phenotypes. In parallel the investigators and others reported that endothelial function, assessed by flow mediated dilatation, is altered in patients with primary and secondary forms of APS. Although a role for TLR (toll-like receptor )-mediated NFkB translocation has been advanced, the pathogenic mechanisms that lead to in vivo endothelial injury in APS are incompletely understood.
In an experimental model, the investigators demonstrated that passive transfer of human aPL to mice induced a marked endothelial dysfunction assessed ex vivo in small resistance arteries, and an increase in TNFα levels. Moreover, the investigators group have demonstrated that patients with primary arterial APS display endothelial dysfunction and structural arterial changes, associated with a pro-oxidative and pro-coagulant state and with activation of the TLR2 and TLR4 signalling pathways.
Recently, in a preliminary study the investigators have found that endothelial glycocalyx which is an important part of the vascular barrier and which is intimately linked to the homeostatic functions of the endothelium was altered in APL patients.
Hydroxychloroquine (HCQ) is an antimalarial drug, also used to treat rheumatic diseases such as SLE. There is experimental evidence to suggest a direct role of hydroxychloroquine on the pathophysiology of APS: it directly reduces the binding of antibodies on the phospholipid bilayers, protects the annexin A5 anticoagulant shield and it reverses platelet adhesion induced by aPL.
Furthermore it is known to decrease the expression of lysosomal TLRs, but also extra lysosomal TLR2 and TLR4.
The aim of this study is to investigate whether treatment with hydroxychloroquine modulates vascular endothelial function in patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| hydroxychlorquine | Experimental | Drug: Hydroxychloroquinehydroxychloroquine 200 mg twice a day for 6 months |
| control | Placebo comparator | Drug: placeboplacebo 2 pills a day for 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients who fulfilled Sidney criteria for APS (antiphospholipid Syndrome
- Women of childbearing potential must have a contraceptive method
- Written informed consent
- no severe, progressive, or uncontrolled kidney, liver, blood, stomach, lung, heart, or brain disease.
Key exclusion criteria (14 listed)
- secondary antiphospholipid syndrome
- Pregnancy and breastfeeding
- Patients with a history of severe depression, psychosis, or suicidal ideation
- story of intolerance or contra-indication to hydroxychloroquine, lactose, trinitrin
- Prior use of hydroxychloroquine in the last 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxychloroquineAlso: plaquenilendothelial function is assessed by measuring the flow mediated dilatation of humeral artery in response to ischemia. the dilatation is evaluated by echotracking. glycocalyx thickness is measured by the study of sublingual microcirculation with SDF imaging. oxydative, inflammatory and coagulation parameters is assessed on plasma samples. | Drug | hydroxychlorquine |
| placeboendothelial function is assessed by measuring the flow mediated dilatation of humeral artery in response to ischemia. the dilatation is evaluated by echotracking. glycocalyx thickness is measured by the study of sublingual microcirculation with SDF imaging. oxydative, inflammatory and coagulation parameters is assessed on plasma samples. | Drug | control |
Primary outcome
Change from baseline flow mediated dilatation of brachial artery
Time frame: 6 months
The brachial artery diameter and blood flow are measured by echotracking and Doppler before and just after and ischemic test. Result expressed in percentage of diameter variation.
5 secondary outcomes
change from baseline in endothelial glycocalyx thickness
Time frame: 6 months
change from baseline in oxydative stress
Time frame: 6 months
change from baseline in systemic inflammation
Time frame: 6 months
change from baseline in coagulation parameter
Time frame: 6 months
change from baseline in plasmatic level in hydroxychloroquine
Time frame: 6 months
Results and safety
The study was stopped early (reason given: Difficulty in enrolling new patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sébastien MIRANDA, MD principal investigator
University Hospital, Rouen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydroxychloroquine in people with Antiphospholipid Syndrome (APS), run by University Hospital, Rouen at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Difficulty in enrolling new patients). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline flow mediated dilatation of brachial artery (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2026.