Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202104858485905 Date of Approval: 06/04/2021
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Hydroxychloroquine Therapy In Women With Autoimmune Recurrent pregnancy Loss Refractory To Low Dose Aspirin And Heparin
Official scientific title Hydroxychloroquine Therapy In Women With Autoimmune Recurrent pregnancy Loss Refractory To Low Dose Aspirin And Heparin
Brief summary describing the background and objectives of the trial This RCT study is aimed to assess pregnancy outcome in women, with a history of autoimmune-related recurrent pregnancy loss refractory to standard treatment (low dose aspirin and heparin ) only, who will be treated with hydroxychloroquine in addition to standard treatment preconception and during pregnancy. Each step in the establishment of normal pregnancy has been implicated as a possible site of immune-mediated reproductive failure. Both autoimmune and alloimmune mechanisms have been proposed. Since the mechanisms that allow a mother to tolerate her semi-allogeneic conceptus are not well defined, it is difficult to assess the role of aberrant immunologic factors in reproductive failure. Several autoimmune diseases have been linked to poor obstetric outcomes, but antiphospholipid syndrome (APS) is the only immune condition in which pregnancy loss is a diagnostic criterion for the disease. Five to 15 percent of patients with RPL may have APS . We selected women according to the history of recurrent pregnancy loss only depending on obstetric morbidity criteria of APS to avoid false-negative results of APL ( seronegative APS).
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Obstetrics and Gynecology
Sub-Disease(s) or condition(s) being studied Fertility-female
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/01/2019
Actual trial start date 01/02/2019
Anticipated date of last follow up 01/12/2020
Actual Last follow-up date 01/01/2021
Anticipated target sample size (number of participants) 120
Actual target sample size (number of participants)
Recruitment status Closed to recruitment,follow-up continuing
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Masking/blinding used Outcome Assessors
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Hydroxychloroquine Hydroxychloroquine 200 mg twice daily twice daily, 81 mg Aspirin, and thromboprophylaxis dose ( according to weight) of LMWH Hydroxychloroquine 200 mg twice daily, starting minimum 2 months (recommended 3-6) prior to conception and continuing until the pregnancy is over. When a woman conceives and after documentation of fetal life, she will contact the study team and attend her first pregnancy visit (first-trimester visit). At this visit, a new trial medication will be dispensed and standard treatment will be started ( 81 mg Aspirin and LMWH in thromboprophylaxis dose according to patient weight ). 1 Informed consent will be obtained from patients who are invited to participate in the research after an explanation of the benefits and risks of this trial and the patients will be counseled for success and failure rate of this trial. 2 RCT of women with a history of autoimmune recurrent pregnancy loss and who planning to conceive. Patients will be randomized to group A or B in addition to their usual medication. Once a woman is enrolled in the study, she will be attending 3 monthly follow-up visits until she conceives (defined as pre-pregnancy visits). 3 Women in the study will take a placebo twice daily, starting a minimum of 2 months (recommended 3-6) prior to conception and continuing until the pregnancy is over. 4 Study visits coincide with the usual routine follow-up visits. On these visits, compliance will be assessed and all data will be collected in an electronic case record file. 5 When a woman conceives and after documentation of fetal life, she will contact the study team and attend her first pregnancy visit (first-trimester visit). At this visit, a new trial medication will be dispensed and standard treatment will be started ( 81 mg Aspirin and LMWH in thromboprophylaxis dose according to patient weight ). Follow-up visits will be scheduled once every three weeks in 1st trimester, one every two weeks in 2nd trimester, and once weekly in the third trimester. 6 Women will be instructed to stop trial medication on the day of delivery and will be asked to hand in the rest of the trial medication at their postpartum follow-up. The postpartum visit shall be completed at 6 weeks postpartum. 60
Control Group placebo and Aspirin and LMWH placebo twice daily, 81 mg Aspirin, and thromboprophylaxis dose ( according to weight) of LMWH placebo twice daily, starting minimum 2 months (recommended 3-6) prior to conception and continuing until the pregnancy is over. When a woman conceives and after documentation of fetal life, she will contact the study team and attend her first pregnancy visit (first-trimester visit). At this visit, a new trial medication will be dispensed and standard treatment will be started ( 81 mg Aspirin and LMWH in thromboprophylaxis dose according to patient weight ). 1 Informed consent will be obtained from patients who are invited to participate in the research after an explanation of the benefits and risks of this trial and the patients will be counseled for success and failure rate of this trial. 2 RCT of women with a history of autoimmune recurrent pregnancy loss and who planning to conceive. Patients will be randomized to group A or B in addition to their usual medication. Once a woman is enrolled in the study, she will be attending 3 monthly follow-up visits until she conceives (defined as pre-pregnancy visits). 3 Women in the study will take a placebo twice daily, starting a minimum of 2 months (recommended 3-6) prior to conception and continuing until the pregnancy is over. 4 Study visits coincide with the usual routine follow-up visits. On these visits, compliance will be assessed and all data will be collected in an electronic case record file. 5 When a woman conceives and after documentation of fetal life, she will contact the study team and attend her first pregnancy visit (first-trimester visit). At this visit, a new trial medication will be dispensed and standard treatment will be started ( 81 mg Aspirin and LMWH in thromboprophylaxis dose according to patient weight ). Follow-up visits will be scheduled once every three weeks in 1st trimester, one every two weeks in 2nd trimester, and once weekly in the third trimester. 6 Women will be instructed to stop trial medication on the day of delivery and will be asked to hand in the rest of the trial medication at their postpartum follow-up. The postpartum visit shall be completed at 6 weeks postpartum. 60 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1) Women, with a history of autoimmune-related recurrent pregnancy loss refractory to standard treatment only, which have had : (a) One or more unexplained deaths of morphologically normal fetuses at or after 10 weeks gestation after documentation of fetal life. (b) One or more premature births of morphologically normal fetuses at or before 34 weeks gestation because of eclampsia or severe preeclampsia or features consistent with placental insufficiency. (c) Three or more consecutive, unexplained spontaneous abortions before 10 weeks gestation, after exclusion of maternal anatomic or hormonal and couple chromosomal abnormalities. 2) Age 18-45 years 3) Body Weight >45 kg 1. Pregnant woman 2. Abnormal uterine anomalies at hysterosalpingography/hysteroscopy or hydrosonography 3. Karyotyping abnormalities within the couple 4. Thyroid dysfunction (hypothyroidism or hyperthyroidism or antithyroid Abs) 5. Other medical morbidity affecting fetal outcome e.g DM and hypertension. 6. Allergy or adverse event to HCQ. Hypersensitivity to the active substance, 4-aminoquinoline or any of the compounds of the IMP or placebo 7. Current treatment with HCQ 8. Body weight<45 kg 9. Psoriasis 10. Uncontrolled epilepsy 11. Other severe active comorbidities (human immunodeficiency virus, hepatitis B) 12. History of retinopathy 13. Previous pregnancy failure on HCQ Adult: 19 Year-44 Year 18 Year(s) 45 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 16/09/2019 Ain Shams University Faculty of Medicine Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Ain Shams University Faculty of Medicine, Abbasia, Cairo, Egypt Cairo 11566 Egypt
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The main outcome was the rate of live births with or without hydroxychloroquine when the pregnancy is over
Secondary Outcome 1 Gestational age at delivery 2 Rate of miscarriage with or without hydroxychloroquine. 3 Birth weight 4 Mode of delivery either vaginal delivery or c.s 5 Apgar score <7 at 5 minutes 6 Neonatal morbidity (bleeding or thrombotic complications, infections, congenital abnormalities) 7 Days to hospital discharge following delivery(mother and neonate) 8 Thrombotic events in the mother during pregnancy and 6 weeks postpartum 9 Days of the neonate in special care. when pregnancy is over , when neonate is discharged from NICU , when patient is discharged from hospital
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Ainshams University Maternity Hospital Faculty of Medicine, Ain Shams University, Ramses street, Abbasseya Cairo 11566 Egypt
FUNDING SOURCES
Name of source Street address City Postal code Country
Mohmmed Ahmed Mohammed Ahmed Abdelrazeq Maternity Hospital, Ain Shams University, Faculty of Medicine, Abbasia, Cairo cairo 11566 Egypt
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Maternity Hospital Faculty of Medicine Ain Shams University Maternity Hospital, Faculty of Medicine, Ain Shams University, Abbasia, Cairo cairo 11566 Egypt Hospital
COLLABORATORS
Name Street address City Postal code Country
Salah Taha Ahmed Fayed Ain Shams University Faculty of Medicine, Department of obstetric and gynecology, Abbaseya cairo 11566 Egypt
Mohammed Salah Elsayed Elsokkary Ain Shams University Faculty of Medicine, Department of Obstetrics and Gynecology, Abbaseya cairo 11566 Egypt
Mohamed Abd Alfattah Elsenity Ain Shams University Faculty of Medicine, Department of Obstetrics and Gynecology, Abbaseya cairo 11566 Egypt
Mahmoud Mohamed Ghaleb Ain Shams University Faculty of Medicine, Department of Obstetrics and Gynecology, Abbaseya cairo 11566 Egypt
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Mohammed Abdelrazeq rizo1411@med.asu.edu.eg +201111600362 Department of Obstetrics and Gynecology, Faculty of Medicine Ain Shams University
City Postal code Country Position/Affiliation
cairo 11566 Egypt Assistant Lecturer in Department of Obstetrics and Gynecology at Faculty of Medicine Ain Shams University
Role Name Email Phone Street address
Scientific Enquiries Salah Fayed salah.t.fayed@gmail.com +201001403176 Department of Obstetrics and Gynecology, Faculty of Medicine Ain Shams University
City Postal code Country Position/Affiliation
cairo 11566 Egypt Professor in department of Obstetrics and Gynecology at Faculty of Medicine Ain Shams University
Role Name Email Phone Street address
Public Enquiries Mohammed Abdelrazeq rizo1411@med.asu.edu.eg +201111600362 Department of Obstetrics and Gynecology, Faculty of Medicine Ain Shams University
City Postal code Country Position/Affiliation
cairo 11566 Egypt Assistant Lecturer in department of Obstetric and Gynecology at Faculty of MedicineAin Shams University
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Data from the study will be available for sharing upon request after the publication of the study within 1 year for a period to be determined by collaborators afterwards. Data will be deidentified and provided after reviewing of submitted proposals by collaborators. Study Protocol Within a year of publication of the study Researchers who provide a methodologically sound proposal, ethical committee approval, and trial registry number will contact the corresponding author or PI within a year of publication and data will be shared after deidentification (tables, figures, appendices..., etc.). Requests will be reviewed as per request by collaborators. Data can be used for meta-analyses or to fulfil asks of submitted proposals. A data access agreement will have to be signed.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information