Antiphospholipid SyndromePhase 4NCT04624269
A Study of Hydroxychloroquine Sulfate in the Treatment of Recurrent Spontaneous Abortion With Antiphospholipid Syndrome
A Phase 4 study testing Hydroxychloroquine Sulfate Tablets in people with Antiphospholipid Syndrome and Recurrent Miscarriage, run by Shanghai First Maternity and Infant Hospital at 1 site in China.
Trial summary
The efficacy of low-dose aspirin combined with low-molecular-weight heparin treatment for improving antiphospholipid syndrome and maternal-fetal outcome of patients is recognized by various countries and recommended by the guidelines. However, there are still 20-30% of APS patients whose treatment fails. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Antiphospholipid Syndrome, Recurrent Miscarriage
- What is being tested?
- Hydroxychloroquine Sulfate Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 384 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2020to 1 Feb 2023
- Phase
- Phase 4
- 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 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Patients who want to conceive，with recurrent miscarriage and antiphospholipid syndrome (APS) .
- Agree to join the study and sign the informed consent of the study.
Who cannot join
- Women who are already pregnant.
- Allergies or adverse events to Hydroxychloroquine(HCQ),such as allergies to the active substance -aminoquinoline or allergies to HCQ or any other chemical components of placebo.
- Patients with any changes in the retina or visual field caused by treatment with 4-aminoquinoline compounds;
- HCQ is currently being used
- Weight <45kg
- Psoriasis
Show all 16Show fewer
- Uncontrolled epilepsy
- Anti-ENA antibody positive
- Renal replacement therapy
- Other serious active complications (human immunodeficiency virus, hepatitis B)
- Porphyria
- History of retinopathy
- History of galactose intolerance, history of lactase deficiency, or history of glucose-galactose malabsorption
- Participate in any other clinical trial drug research at the same time.
- Previous treatment failure with Hydroxychloroquin
- Others: such as poor compliance, or those who cannot be followed up on schedule due to certain factors.
Trial locations and contacts
1 site in 1 country.
China1 site
shanghai First Maternity and Infant Hospital, Tongji University School of Medicin
Shanghai
Shihua Bao, 86-021-20261599, baoshihua@tongji.edu.cn
About this study
Official title: A Multicenter, Double-blind, Randomized and Parallel Controlled Study of Hydroxychloroquine Sulfate in the Treatment of Recurrent Miscarriage With Antiphospholipid Syndrome
The efficacy of low-dose aspirin combined with low-molecular-weight heparin treatment for improving antiphospholipid syndrome and maternal-fetal outcome of patients is recognized by various countries and recommended by the guidelines. However, there are still 20-30% of APS patients whose treatment fails. Therefore, the standard treatment effect is still not ideal, and other treatment options need to be explored. The purpose of this study is to conduct a randomized double-blind, parallel controlled study of patients with recurrent miscarriage and APS in addition to standard treatment, plus hydroxychloroquine sulfate (HCQ) or placebo, to observe the effects of HCQ on pregnancy outcome in patients with abortion and APS, to evaluate the effectiveness and safety of HCQ treatment.
Read the detailed description
This study uses a multi-center, double-blind, randomized, parallel-controlled research model. In addition to the standard anticoagulant drugs for antiphospholipid syndrome, patients with recurrent miscarriage and APS who meet the enrollment criteria will be randomly divided into hydroxychloroquine sulfate( HCQ) group or placebo group, and randomly assigned according to a 1:1 ratio. Observe the efficacy and safety.
The Hydroxychloroquine sulfate(HCQ) group is the test group. Hydroxychloroquine sulfate 0.2g/d (sig: 0.1g bid po) will be applied 3 months before pregnancy, pregnancy will be started at the 4th month, and aspirin 50mg/d will be added after menstruation( sig: 25mg bid po), low molecular weight heparin 4000-6000 U/d after ovulation or 1 week before embryo transplantation; the placebo group is the control group, and placebo 0.2g/d (sig: 0.1 g bid po) from the fourth month of pregnancy, add aspirin 50mg/d (sig: 25mg bid po) after menstruation, and add low molecular heparin 4000-6000 U/d after ovulation or 1 week before embryo transplantation Both groups were followed up by telephone every 1 month to obtain medication compliance, whether there were adverse reactions, etc., and both oth groups were followed up every 3 months for non-pregnant women by outpatient service , until pregnancy. If the patient is not pregnant within one year, The clinical study of this patient will be terminated, and the patients will be followed up for adverse reactions by telephone one month and three months after withdrawal. If you are pregnant, follow up in the first trimester immediately, and arrange a follow-up every three months thereafter (defined as follow-up in the first trimester, follow-up in the second trimester and follow-up in the third trimester). The drug was discontinued on the day of delivery and the postpartum follow-up was completed 6 weeks after delivery. So, therefore, the entire study time is approximately 27 months.
The researcher mainly records the subjects' vital signs, laboratory indicators, adverse events and combined medications, as well as related indicators of pregnancy check-ups (such as uterine artery blood flow, presence or absence of pregnancy complications, fetal complications, etc.)
- Conditions
- Antiphospholipid Syndrome, Recurrent Miscarriage
- Being tested
- Hydroxychloroquine Sulfate Tablets
- Keywords
- Antiphospholipid syndrome, hydroxychloroquine, Recurrent Miscarriage
- Medical subject headings
- Antiphospholipid Syndrome, Abortion, Habitual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxychloroquine Sulfate TabletsDrug
Also called Fenle
Hydroxychloroquine Sulfate Tablets ,0.1mg，bid po
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine sulfate Tablets | Experimental | drug:Hydroxychloroquine sulfate Tablets,0.1mg bid po Receives: Drug: Hydroxychloroquine Sulfate Tablets |
| placebo | Placebo comparator | drug:placebo,0.1mg bid po Receives: Drug: Hydroxychloroquine Sulfate Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hydroxychloroquine can improve the pregnancy outcome of patients with recurrent miscarriage and antiphospholipid syndrome
Hydroxychloroquine is associated with successful pregnancy outcome at 12 weeks of gestation
Measured: 16 weeks
Secondary outcomes (1)
Hydroxychloroquine can reduce the occurrence of complications during pregnancy
Reduced incidence of major adverse pregnancy outcomes related to antiphospholipid syndrome
Measured: 27 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2020
- Study start1 Dec 2020 (estimated)
- Primary completion1 Nov 2021 (estimated)
- Study completion1 Feb 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Antiphospholipid SyndromeStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 384 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai First Maternity and Infant Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Fudan University, Zhejiang Provincial People's Hospital, Zhejiang Provincial Tongde Hospital
- Responsible party
- Sponsor
- Investigators
- Bao shihua, doctor, Study chair, shanghai First Maternity and Infant Hospital, Tongji University School of Medicin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04624269
- Sponsor's protocol ID
- ShanghaiFMIH-HCQ
- Status last verified
- Nov 2020
- First submitted
- 31 Oct 2020
- Last updated
- 10 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mak A, Cheung MW, Cheak AA, Ho RC. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology (Oxford). 2010 Feb;49(2):281-8. doi: 10.1093/rheumatology/kep373. Epub 2009 Dec 4.
PubMed 19965971Sciascia S, Branch DW, Levy RA, Middeldorp S, Pavord S, Roccatello D, Ruiz-Irastorza G, Tincani A, Khamashta M, Schreiber K, Hunt BJ. The efficacy of hydroxychloroquine in altering pregnancy outcome in women with antiphospholipid antibodies. Evidence and clinical judgment. Thromb Haemost. 2016 Jan;115(2):285-90. doi: 10.1160/TH15-06-0491. Epub 2015 Sep 17.
PubMed 26421409Abarientos C, Sperber K, Shapiro DL, Aronow WS, Chao CP, Ash JY. Hydroxychloroquine in systemic lupus erythematosus and rheumatoid arthritis and its safety in pregnancy. Expert Opin Drug Saf. 2011 Sep;10(5):705-14. doi: 10.1517/14740338.2011.566555. Epub 2011 Mar 22.
PubMed 21417950Mekinian A, Lazzaroni MG, Kuzenko A, Alijotas-Reig J, Ruffatti A, Levy P, Canti V, Bremme K, Bezanahary H, Bertero T, Dhote R, Maurier F, Andreoli L, Benbara A, Tigazin A, Carbillon L, Nicaise-Roland P, Tincani A, Fain O; SNFMI and the European Forum on Antiphospholipid Antibodies. The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: Data from a European multicenter retrospective study. Autoimmun Rev. 2015 Jun;14(6):498-502. doi: 10.1016/j.autrev.2015.01.012. Epub 2015 Jan 21.
PubMed 25617818Branch DW, Peaceman AM, Druzin M, Silver RK, El-Sayed Y, Silver RM, Esplin MS, Spinnato J, Harger J. A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group. Am J Obstet Gynecol. 2000 Jan;182(1 Pt 1):122-7. doi: 10.1016/s0002-9378(00)70500-x.
PubMed 10649166Sciascia S, Hunt BJ, Talavera-Garcia E, Lliso G, Khamashta MA, Cuadrado MJ. The impact of hydroxychloroquine treatment on pregnancy outcome in women with antiphospholipid antibodies. Am J Obstet Gynecol. 2016 Feb;214(2):273.e1-273.e8. doi: 10.1016/j.ajog.2015.09.078. Epub 2015 Sep 30.
PubMed 26429521
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Double-blind, Randomized and Parallel Controlled Study of Hydroxychloroquine Sulfate in the Treatment of Recurrent Miscarriage With Antiphospholipid Syndrome
- ClinicalTrials.gov ID
- NCT04624269
- Acronym / sponsor ID
- ShanghaiFMIH-HCQ
- Conditions
- Antiphospholipid Syndrome, Recurrent Miscarriage
- Keywords
- Antiphospholipid syndrome, hydroxychloroquine, Recurrent Miscarriage
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 384 participants (estimated)
- Lead sponsor
- Shanghai First Maternity and Infant HospitalUniversity, hospital or other
- Collaborators
- Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Fudan University, Zhejiang Provincial People's Hospital, Zhejiang Provincial Tongde Hospital
- Study start
- 1 Dec 2020 (estimated)
- Primary completion
- 1 Nov 2021 (estimated)
- Study completion
- 1 Feb 2023 (estimated)
- First posted
- 10 Nov 2020 (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.
The efficacy of low-dose aspirin combined with low-molecular-weight heparin treatment for improving antiphospholipid syndrome and maternal-fetal outcome of patients is recognized by various countries and recommended by the guidelines. However, there are still 20-30% of APS patients whose treatment fails. Therefore, the standard treatment effect is still not ideal, and other treatment options need to be explored. The purpose of this study is to conduct a randomized double-blind, parallel controlled study of patients with recurrent miscarriage and APS in addition to standard treatment, plus hydroxychloroquine sulfate (HCQ) or placebo, to observe the effects of HCQ on pregnancy outcome in patients with abortion and APS, to evaluate the effectiveness and safety of HCQ treatment.
Detailed description
This study uses a multi-center, double-blind, randomized, parallel-controlled research model. In addition to the standard anticoagulant drugs for antiphospholipid syndrome, patients with recurrent miscarriage and APS who meet the enrollment criteria will be randomly divided into hydroxychloroquine sulfate( HCQ) group or placebo group, and randomly assigned according to a 1:1 ratio. Observe the efficacy and safety.
The Hydroxychloroquine sulfate(HCQ) group is the test group. Hydroxychloroquine sulfate 0.2g/d (sig: 0.1g bid po) will be applied 3 months before pregnancy, pregnancy will be started at the 4th month, and aspirin 50mg/d will be added after menstruation( sig: 25mg bid po), low molecular weight heparin 4000-6000 U/d after ovulation or 1 week before embryo transplantation; the placebo group is the control group, and placebo 0.2g/d (sig: 0.1 g bid po) from the fourth month of pregnancy, add aspirin 50mg/d (sig: 25mg bid po) after menstruation, and add low molecular heparin 4000-6000 U/d after ovulation or 1 week before embryo transplantation Both groups were followed up by telephone every 1 month to obtain medication compliance, whether there were adverse reactions, etc., and both oth groups were followed up every 3 months for non-pregnant women by outpatient service , until pregnancy. If the patient is not pregnant within one year, The clinical study of this patient will be terminated, and the patients will be followed up for adverse reactions by telephone one month and three months after withdrawal. If you are pregnant, follow up in the first trimester immediately, and arrange a follow-up every three months thereafter (defined as follow-up in the first trimester, follow-up in the second trimester and follow-up in the third trimester). The drug was discontinued on the day of delivery and the postpartum follow-up was completed 6 weeks after delivery. So, therefore, the entire study time is approximately 27 months.
The researcher mainly records the subjects' vital signs, laboratory indicators, adverse events and combined medications, as well as related indicators of pregnancy check-ups (such as uterine artery blood flow, presence or absence of pregnancy complications, fetal complications, etc.)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine sulfate Tablets | Experimental | Drug: Hydroxychloroquine Sulfate Tabletsdrug:Hydroxychloroquine sulfate Tablets,0.1mg bid po |
| placebo | Placebo comparator | Drug: Hydroxychloroquine Sulfate Tabletsdrug:placebo,0.1mg bid po |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Patients who want to conceive，with recurrent miscarriage and antiphospholipid syndrome (APS) .
- Agree to join the study and sign the informed consent of the study.
Key exclusion criteria (16 listed)
- Women who are already pregnant.
- Allergies or adverse events to Hydroxychloroquine(HCQ),such as allergies to the active substance -aminoquinoline or allergies to HCQ or any other chemical components of placebo.
- Patients with any changes in the retina or visual field caused by treatment with 4-aminoquinoline compounds;
- HCQ is currently being used
- Weight <45kg
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 |
|---|---|---|
| Hydroxychloroquine Sulfate TabletsAlso: FenleHydroxychloroquine Sulfate Tablets ,0.1mg，bid po | Drug | Hydroxychloroquine sulfate Tablets, placebo |
Primary outcome
Hydroxychloroquine can improve the pregnancy outcome of patients with recurrent miscarriage and antiphospholipid syndrome
Time frame: 16 weeks
Hydroxychloroquine is associated with successful pregnancy outcome at 12 weeks of gestation
1 secondary outcome
Hydroxychloroquine can reduce the occurrence of complications during pregnancy
Time frame: 27 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2020.
- Background: PubMed 19965971Mak A, Cheung MW, Cheak AA, Ho RC. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology (Oxford). 2010 Feb;49(2):281-8. doi: 10.1093/rheumatology/kep373. Epub 2009 Dec 4.
- Results publication: PubMed 26421409Sciascia S, Branch DW, Levy RA, Middeldorp S, Pavord S, Roccatello D, Ruiz-Irastorza G, Tincani A, Khamashta M, Schreiber K, Hunt BJ. The efficacy of hydroxychloroquine in altering pregnancy outcome in women with antiphospholipid antibodies. Evidence and clinical judgment. Thromb Haemost. 2016 Jan;115(2):285-90. doi: 10.1160/TH15-06-0491. Epub 2015 Sep 17.
- Results publication: PubMed 21417950Abarientos C, Sperber K, Shapiro DL, Aronow WS, Chao CP, Ash JY. Hydroxychloroquine in systemic lupus erythematosus and rheumatoid arthritis and its safety in pregnancy. Expert Opin Drug Saf. 2011 Sep;10(5):705-14. doi: 10.1517/14740338.2011.566555. Epub 2011 Mar 22.
- Results publication: PubMed 25617818Mekinian A, Lazzaroni MG, Kuzenko A, Alijotas-Reig J, Ruffatti A, Levy P, Canti V, Bremme K, Bezanahary H, Bertero T, Dhote R, Maurier F, Andreoli L, Benbara A, Tigazin A, Carbillon L, Nicaise-Roland P, Tincani A, Fain O; SNFMI and the European Forum on Antiphospholipid Antibodies. The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: Data from a European multicenter retrospective study. Autoimmun Rev. 2015 Jun;14(6):498-502. doi: 10.1016/j.autrev.2015.01.012. Epub 2015 Jan 21.
- Results publication: PubMed 10649166Branch DW, Peaceman AM, Druzin M, Silver RK, El-Sayed Y, Silver RM, Esplin MS, Spinnato J, Harger J. A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group. Am J Obstet Gynecol. 2000 Jan;182(1 Pt 1):122-7. doi: 10.1016/s0002-9378(00)70500-x.
- Results publication: PubMed 26429521Sciascia S, Hunt BJ, Talavera-Garcia E, Lliso G, Khamashta MA, Cuadrado MJ. The impact of hydroxychloroquine treatment on pregnancy outcome in women with antiphospholipid antibodies. Am J Obstet Gynecol. 2016 Feb;214(2):273.e1-273.e8. doi: 10.1016/j.ajog.2015.09.078. Epub 2015 Sep 30.
- 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.
Bao shihua, doctor study chair
shanghai First Maternity and Infant Hospital, Tongji University School of Medicin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hydroxychloroquine Sulfate Tablets in people with Antiphospholipid Syndrome and Recurrent Miscarriage, run by Shanghai First Maternity and Infant Hospital at 1 site in China.
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 2 inclusion and 16 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 10 Nov 2020. 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 China. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Du mengyang, Master (0086-13636467524, dumengyanga@51mch.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hydroxychloroquine can improve the pregnancy outcome of patients with recurrent miscarriage and antiphospholipid syndrome (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04624269, which also lists 6 linked publications.
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 10 Nov 2020.