A three-arm, multicenter, open-label randomized controlled trial of hydroxychloroquine and low-dose prednisone to treat recurrent pregnancy loss in women with undifferentiated connective tissue diseases: Protocol for the immunosuppressant regimens for Living FEtuses (ILIFE) Trial

Abstract

Background: Undifferentiated connective tissue disease (UCTD) is known to induce adverse pregnancy outcomes, and even recurrent spontaneous abortion (RSA) by placental vascular damage and inflammation activation. Anticoagulation can prevent pregnancy morbidities. However, it is unknown whether the addition of immune suppressant to anticoagulation can prevent spontaneous pregnancy loss in UCTD patients. The purpose of this study is to evaluate the efficacy of hydroxychloroquine (HCQ) and low-dose prednisone on recurrent pregnancy loss for women with UCTD.Methods: The Immunosuppressant for Living Fetuses (ILIFE) Trial is a three-arm, multicenter, open-label randomized controlled trial with the primary objective of comparing hydroxychloroquine combined with low-dose prednisone and anticoagulation with anticoagulation alone in treating UCTD women with recurrent spontaneous abortion. The third arm of using hydroxychloroquine combined with anticoagulant for secondary comparison. A total of 426 eligible patients will be randomly assigned to each of the three arms with a 1:1:1 allocation ratio. The primary outcome is the rate of live births. Secondary outcomes include adverse pregnancy outcomes and progression of UCTD.Discussion: This is the first multi-center, open-label, randomized controlled trial which evaluates the efficacy of immunosuppressant regimens on pregnancy outcomes and UCTD progression. It will provide evidence on whether the immunosuppressant ameliorates the pregnancy prognosis in UCTD patients with RSA and the progression into defined connective tissue disease. Trial registration: ClinicalTrials.gov, NCT03671174. Registered on 14 September 2018. https://www.clinicaltrials.gov/ct2/show/NCT03671174

Recent Advances in Immunotherapeutic Approaches for Recurrent Reproductive Failure

“…Hydroxychloroquine administration for autoimmune-related RPL women who did not gain benefit of the low-dose aspirin and LMWH in previous pregnancies, indicated that hydroxychloroquine was able to significantly increase the live birth rate, gestational age at delivery and the mean birth weight, in comparison to placebo group [164]. There are some ongoing clinical trials assessing the impact of hydroxychloroquine on RPL or RM women [165][166][167]. Nevertheless, the results of a systematic review by Yang et al suggested that combination of hydroxychloroquine with current treatment regimens used in the prevention of RM in APS patients, including low-dose aspirin and heparin, has been shown to have beneficial effects.…”

The place of hydroxychloroquine in modern dermatology

“…The effectiveness of HCQ in slowing the progression of UCTD to SLE was suggested based on a retrospective analysis [55]. Two RCTs are currently underway to determine the effectiveness of HCQ in MCTD and UCTD [56,57].…”

“…Skuteczność HCQ w spowolnieniu progresji UCTD do SLE sugerowano na podstawie analizy retrospektywnej [55]. Aktualnie prowadzone są RCT mające na celu potwierdzenie skuteczności HCQ w MCTD i UCTD [56,57].…”