Design and Protocol of the Renal Anhydramnios Fetal Therapy (RAFT) Trial

Abstract

Purpose: Anhydramnios secondary to anuria before 22 weeks of gestational age and congenital bilateral renal agenesis before 26 weeks of gestational age are collectively referred to as early-pregnancy renal anhydramnios. Early-pregnancy renal anhydramnios occurs in at least 1 in 2000 pregnancies and is considered universally fatal when left untreated because of severe pulmonary hypoplasia precluding ex utero survival The Renal Anhydramnios Fetal Therapy (RAFT) trial is a nonrandomized, nonblinded, multicenter clinical trial designed to assess the efficacy, safety, and feasibility of amnioinfusions for patients with pregnancies complicated by early-pregnancy renal anhydramnios. The primary objective of this study is to determine the proportion of neonates surviving to successful dialysis, defined as use of a dialysis catheter for ≥14 days.

Methods: A consortium of 9 North American Fetal Therapy Network (NAFTNet) centers was formed, and the RAFT protocol was refined in collaboration with the NAFTNet Scientific Committee. Enrollment in the trial began in April 2020. Participants may elect to receive amnioinfusions or to join the nonintervention observational expectant management group. Eligible pregnant women must be at least 18 years of age with a fetal diagnosis of isolated early-pregnancy renal anhydramnios.

Findings: In addition to the primary study objective stated above, secondary objectives include (1) to assess maternal safety and feasibility of the serial amnioinfusion intervention (2) to perform an exploratory study of the natural history of untreated early pregnancy renal anhydramnios (3) to examine correlations between prenatal imaging and lung specific factors in amniotic fluid as predictive of the efficacy of serial percutaneous amnioinfusions and (4) to determine short- and long-term outcomes and quality of life in surviving neonates and families enrolled in RAFT IMPLICATIONS: The RAFT trial is the first clinical trial to investigate the efficacy, safety, and feasibility of amnioinfusions to treat the survival-limiting pulmonary hypoplasia associated with anhydramnios. Although the intervention offers an opportunity to treat a condition known to be almost universally fatal in affected neonates, the potential burdens associated with end-stage kidney disease from birth must be acknowledged.

Clinicaltrials: gov identifier: NCT03101891.

Keywords: Potter syndrome; amnioinfusion; anhydramnios; fetal renal failure; pulmonary hypoplasia; renal agenesis.

Figure 1.

Study Design. Patients referred to Renal Anhydramnios Fetal Therapy (RAFT) trial center for suspicion of early pregnancy renal anhydramnios (EPRA) will undergo counseling and a diagnostic amnioinfusion. If the diagnosis is confirmed (anhydramnios in the absence of ruptured membranes and absent bladder filling) inclusion and exclusion criteria will be applied (see Table 2). If the parents do not wish to be a part of the study, standard prenatal care will be offered. Once enrolled in the study, participants will have the choice of expectant management or serial amnioinfuslons. Those In the intervention group will be allowed to switch to expectant management If they do not wish to continue amnioinfuslons. All participants will deliver at a RAFT center. They will be enrolled in the North American Renal Trials and Collaborative Studies (NAPRTCS) registry for long-term follow-up in the RAFT trial. FRF=fetal renal failure; Co-BRA=congenltal bilateral renal agenesis; GA=gestational age

Figure 2.

RAFT enrollment model. Explored optimistic (5.5/site-year), at-plan (3.6/site-year) and pessimistic (3/site-year) estimates of combined enrollment rates for the 30 subjects in the expectant management group and 70 subjects in the treatment group. At-plan enrollment completes in 42 months, leaving 18 months of follow-up for the last patient enrolled.

Figure 3.

Timeline of study procedures for intervention group. All study visits including delivery will occur at a RAFT center