Primary Antiphospholipid SyndromePhase 3PAPIRUSNCT03540810
Hydroxychloroquine Versus Placebo: Impact on Thrombotic Relapse in Primary Antiphospholipid Syndrome
A Phase 3 study testing Hydroxychloroquine in people with Primary Antiphospholipid Syndrome, run by University Hospital, Angers at 1 site in France.
Trial summary
Antiphospholipid syndrome (APS) combines thrombotic (venous and/or arterial) and/or obstetrical manifestations, along with biological anomalies related to the presence of antiphospholipid antibodies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Antiphospholipid Syndrome
- What is being tested?
- Hydroxychloroquine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 1 siteFrance
- Study dates
- 15 Aug 2018to 15 Oct 2022
- Phase
- Phase 3
- 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
- Age >18 years
- Presence of a primary antiphospholipid syndrome with previous venous/arterial thrombosis and which needs a treatment with VKA
- Patients with a signed commitment
Who cannot join
- Secondary APS
- Ocular diseases :
- retinal disease contraindicating the prescription of hydroxychloroquine
- cataract
- monophtalmic
- Past history of intolerance or allergy to hydroxychloroquine
Show all 21Show fewer
- Known deficit in G6PDase
- Hemolytic anemia
- Porphyria
- Chronic hepatic disease
- Severe renal failure (creatinin clearence <30ml/min)
- Chronic alcoholism
- Patient with QT interval >440 ms on the ECG
- Concomitant treatment with drugs raising the QT interval
- Epilepsy
- Pregnant or breastfeeding women
- Women refusing an effective contraception
- Active cancer or malignant hemopathy
- Psychiatric disease unabling the compliance to treatment
- Unaffiliated person or not beneficiary of a social security system
- Concomitant participation at a biomedical trial able to interfere with the actual trial
Trial locations and contacts
1 site in 1 country.
About this study
Antiphospholipid syndrome (APS) combines thrombotic (venous and/or arterial) and/or obstetrical manifestations, along with biological anomalies related to the presence of antiphospholipid antibodies. Despite actual treatment recommended by international guidelines, the relapse rate in APS is high and survival is 65% at 15 years. Hydroxychloroquine has demonstrated its efficacy and benefits in the treatment of Systemic Lupus Erythematosus, but there is no current consensus concerning the efficacy of this treatment in the secondary prevention of thrombotic events in primary APS, even though several in vitro experimental and animal model data, along with several clinical studies have suggested a beneficial effect of this drug in this indication. Considering the prevalence of primary APS in the general population and of the number of clinical events observed in patients with primary APS and receiving conventional treatment with vitamin K anticoagulants (VKA), the consortium expects a minimum clinically relevant difference of 70%. Considering a prevalence of thrombotic events for the entire studied primary APS population of 10% at 2 years, the consortium expects a 70% decrease in thrombotic events under Hydroxychloroquine treatment administered in addition to VKA treatment in primary APS, i.e. a 3% prevalence in the Hydroxychloroquine group at 2 years. The consortium proposes a drug trial, phase III, national multicentric, comparative, randomized, superiority, double-blind, controlled with 2 compared groups (Hydroxychloroquine versus placebo) study. The enrolment period will be 24 months.
The main aim of this trial is to comparatively assess at 24 months the number of new thrombotic events (venous and arterial) in primary antiphospholipid syndrome in patients treated with VKA plus Hydroxychloroquine versus VKA plus placebo, in a multicentre, prospective randomized, double-blind, versus placebo study.
- Conditions
- Primary Antiphospholipid Syndrome
- Being tested
- Hydroxychloroquine, Placebo
- Keywords
- antiphospholipid syndrome, thrombosis, hydroxychloroquine
- Medical subject headings
- Antiphospholipid Syndrome, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called HCQ
The patients will additionally receive this drug with their usual treatment to evaluate its efficiency to prevent new thrombotic events in primary antiphospholipid syndrome patients
PlaceboDrug
The patients will receive placebo with their usual treatment
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine | Active comparator | All patients randomised in this arm will receive hydroxychloroquine with their usual treatment, which is antivitamin K anticoagulants Receives: Drug: Hydroxychloroquine |
| Placebo | Placebo comparator | All patients randomised in this arm will receive a placebo with their usual treatment, which is antivitamin K anticoagulants Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of thrombotic events in each arm after 24 months of treatment
The number of thrombotic events will be compared in the two arms of the study. The events which will be considered are deep venous thrombosis, superficial venous thrombosis, lung embolism, stroke, myocardial infarction as assessed by at least one diagnostic tests such as: doppler echography, lung scintigraphy, lung CT scan, cerebral CT scan, cerebral MRI, myocardial scintigraphy, coronarography.
Measured: 24 month
Secondary outcomes (7)
Number of participants with treatment-related adverse events as assessed by CTCAE
The number of participants with treatment-related adverse events as assessed by CTCAE will be compared in the two arms of the study
Measured: 24 month
Number of hospitalizations days related to thrombotic event
The number of hospitalizations days, related to thrombotic event in each arm after 24 months of treatment
Measured: 24 month
Number of work incapacity days related to thrombotic event
The number of work incapacity days, related to thrombotic event in each arm after 24 months of treatment
Measured: 24 month
The specific biological markers of thrombosis in APS such as type and number of antiphospholipid antibodies, complement, antinuclear antibodies, thrombocytosis
The specific biological markers of thrombosis in APS such as type and number of antiphospholipid antibodies, complement, antinuclear antibodies, thrombocytosis in each arm
Measured: 24 month
Assess compliance to VKA
The different recorded values of blood INR all along the study
Measured: 24 month
Assess Assess compliance to HCQ
The values of blood Hydroxychloroquine measured at the end of the 24 months of treatment
Measured: 24 month
The vascular arterial rigidity measured by doppler echography
The vascular arterial rigidity measured by doppler echography will be compared between the two arms of the study at inclusion in the study and after 24 months of treatment
Measured: 24 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2018
- Study start15 Aug 2018 (estimated)
- Primary completion15 Aug 2022 (estimated)
- Study completion15 Oct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Antiphospholipid SyndromeStudies of the same condition, open and under way.
- More trials run by University Hospital, AngersThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Angers
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Cristina Belizna, MD, PhD, Principal investigator, University Hospital, Angers
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03540810
- Sponsor's protocol ID
- 2017-004416-19
- Other IDs
- 2017
- Acronym
- PAPIRUS
- Status last verified
- May 2018
- First submitted
- 27 Apr 2018
- Last updated
- 30 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydroxychloroquine Versus Placebo: Impact on Thrombotic Relapse in Primary Antiphospholipid Syndrome
- ClinicalTrials.gov ID
- NCT03540810
- Acronym / sponsor ID
- PAPIRUS / 2017-004416-19
- Conditions
- Primary Antiphospholipid Syndrome
- Keywords
- antiphospholipid syndrome, thrombosis, hydroxychloroquine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- University Hospital, AngersOther government
- Study start
- 15 Aug 2018 (estimated)
- Primary completion
- 15 Aug 2022 (estimated)
- Study completion
- 15 Oct 2022 (estimated)
- First posted
- 30 May 2018 (actual)
- 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.
Antiphospholipid syndrome (APS) combines thrombotic (venous and/or arterial) and/or obstetrical manifestations, along with biological anomalies related to the presence of antiphospholipid antibodies. Despite actual treatment recommended by international guidelines, the relapse rate in APS is high and survival is 65% at 15 years. Hydroxychloroquine has demonstrated its efficacy and benefits in the treatment of Systemic Lupus Erythematosus, but there is no current consensus concerning the efficacy of this treatment in the secondary prevention of thrombotic events in primary APS, even though several in vitro experimental and animal model data, along with several clinical studies have suggested a beneficial effect of this drug in this indication. Considering the prevalence of primary APS in the general population and of the number of clinical events observed in patients with primary APS and receiving conventional treatment with vitamin K anticoagulants (VKA), the consortium expects a minimum clinically relevant difference of 70%. Considering a prevalence of thrombotic events for the entire studied primary APS population of 10% at 2 years, the consortium expects a 70% decrease in thrombotic events under Hydroxychloroquine treatment administered in addition to VKA treatment in primary APS, i.e. a 3% prevalence in the Hydroxychloroquine group at 2 years. The consortium proposes a drug trial, phase III, national multicentric, comparative, randomized, superiority, double-blind, controlled with 2 compared groups (Hydroxychloroquine versus placebo) study. The enrolment period will be 24 months.
The main aim of this trial is to comparatively assess at 24 months the number of new thrombotic events (venous and arterial) in primary antiphospholipid syndrome in patients treated with VKA plus Hydroxychloroquine versus VKA plus placebo, in a multicentre, prospective randomized, double-blind, versus placebo study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine | Active comparator | Drug: HydroxychloroquineAll patients randomised in this arm will receive hydroxychloroquine with their usual treatment, which is antivitamin K anticoagulants |
| Placebo | Placebo comparator | Drug: PlaceboAll patients randomised in this arm will receive a placebo with their usual treatment, which is antivitamin K anticoagulants |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age >18 years
- Presence of a primary antiphospholipid syndrome with previous venous/arterial thrombosis and which needs a treatment with VKA
- Patients with a signed commitment
Key exclusion criteria (21 listed)
- Secondary APS
- Ocular diseases :
- Past history of intolerance or allergy to hydroxychloroquine
- Known deficit in G6PDase
- Hemolytic anemia
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: HCQThe patients will additionally receive this drug with their usual treatment to evaluate its efficiency to prevent new thrombotic events in primary antiphospholipid syndrome patients | Drug | Hydroxychloroquine |
| PlaceboThe patients will receive placebo with their usual treatment | Drug | Placebo |
Primary outcome
Number of thrombotic events in each arm after 24 months of treatment
Time frame: 24 month
The number of thrombotic events will be compared in the two arms of the study. The events which will be considered are deep venous thrombosis, superficial venous thrombosis, lung embolism, stroke, myocardial infarction as assessed by at least one diagnostic tests such as: doppler echography, lung scintigraphy, lung CT scan, cerebral CT scan, cerebral MRI, myocardial scintigraphy, coronarography.
7 secondary outcomes
Number of participants with treatment-related adverse events as assessed by CTCAE
Time frame: 24 month
Number of hospitalizations days related to thrombotic event
Time frame: 24 month
Number of work incapacity days related to thrombotic event
Time frame: 24 month
The specific biological markers of thrombosis in APS such as type and number of antiphospholipid antibodies, complement, antinuclear antibodies, thrombocytosis
Time frame: 24 month
Assess compliance to VKA
Time frame: 24 month
Assess Assess compliance to HCQ
Time frame: 24 month
The vascular arterial rigidity measured by doppler echography
Time frame: 24 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2018.
- Individual participant dataSharing planned: No
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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.
Cristina Belizna, MD, PhD principal investigator
University Hospital, Angers
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydroxychloroquine in people with Primary Antiphospholipid Syndrome, run by University Hospital, Angers 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 3 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 30 May 2018. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Cristina C Belizna, Coordinator (0033241356592, cristina.belizna@wanadoo.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of thrombotic events in each arm after 24 months of treatment (time frame: 24 month). 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 30 May 2018.