A three-arm, multicenter, open-label randomized controlled trial of hydroxychloroquine and low-dose prednisone on recurrent spontaneous abortion with undifferentiated connective tissue diseases: Protocol for the immunosuppressant regimens for Living FEtuses (ILIFE) Trial

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 of comparing hydroxychloroquine combined with low-dose prednisone and anticoagulation, hydroxychloroquine combined with anticoagulant, or anticoagulation alone in treating UCTD women with recurrent spontaneous abortion. Eligible patients will be randomly assigned to each of the tree 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.