Evaluation of Materno-Fetal Hyperoxygenation with Oxygen Therapy in Third Trimester for Fetal Left Ventricular Hypoplasia Treatment

The primary objective of this clinical trial is to evaluate the **efficacy** of materno-fetal hyperoxygenation (MFHO) during the third trimester of pregnancy on the growth of underdeveloped fetal left ventricular structures. This is clinically relevant as it addresses a developmental disorder of the left side of the heart in unborn babies, potentially improving cardiac development and outcomes in affected fetuses. The study does not list any secondary objectives.

The clinical trial focuses on evaluating the efficacy of **materno-fetal hyperoxygenation** during the third trimester of pregnancy in promoting the growth of underdeveloped fetal left ventricular structures. The study population includes pregnant women aged 18 years and older, specifically in their third trimester, who are non-smokers and have undergone an A. uterina Doppler ultrasound without pathological findings. The trial also involves fetuses diagnosed with a developmental disorder of the left side of the heart, characterized by at least one underdeveloped left ventricular structure, yet maintaining sufficient cardiac function. Both male and female fetuses are included in the study, and the trial population is considered vulnerable. The sponsor has not provided information regarding the total number of participants. Participants were selected based on specific inclusion criteria, ensuring a focus on maternal and fetal health status, with lifestyle considerations such as non-smoking being a key factor.

The clinical trial is a **prospective, randomized, controlled, open, multicenter** study designed to evaluate the efficacy and safety of materno-fetal hyperoxygenation (MFHO) during the third trimester of pregnancy. The primary objective is to assess the impact of MFHO on the growth of underdeveloped fetal left ventricular structures in cases of **hypoplastic left heart syndrome**. The trial is expected to run until September 2028, with recruitment having commenced in August 2023. Participants will be randomly assigned to receive either the intervention or control treatment, ensuring unbiased results.

Study visits are structured to include an initial **screening visit** to confirm eligibility based on criteria such as maternal age (≥18 years), third trimester status, non-smoking status, and specific fetal cardiac conditions. Following the screening, participants will undergo regular follow-up visits to monitor fetal cardiac development and maternal health. The primary endpoint will be evaluated by measuring the median change in the sum of the Z-scores of selected echocardiographic fetal heart structures under oxygen provocation at specific time points. The study will conclude with an **end-of-study visit** to assess the overall outcomes and any potential adverse effects.

Participant involvement is anticipated to last for the duration of the third trimester, with the maximum treatment period set at eight weeks. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or any medical condition that contraindicates continued participation. The trial employs **oxygen** as the active substance, administered via inhalation, with a maximum daily dose of 4320 liters and a total dose limit of 241920 liters. The study is categorized as a Phase III clinical trial, indicating its advanced stage in the clinical research process.

The clinical trial involves the administration of **LOX medicAL 100% (V/V)**, a **medicinal gas, cryogenic** form of **oxygen**. This experimental medication is provided by AIR LIQUIDE MEDICAL GMBH and is intended for **inhalation use**. The maximum daily dose is 4320 liters, with a total maximum dose of 241920 liters over the course of the treatment period. The treatment is designed to be administered over a maximum period of 8 weeks. The primary objective of the trial is to evaluate the efficacy of materno-fetal hyperoxygenation (MFHO) during the third trimester of pregnancy in promoting the growth of underdeveloped fetal left ventricular structures.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of the experimental medicinal gas. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed inhalation regimen. The trial is structured to provide evidence on the safety and efficacy of the treatment, with careful monitoring of all participants to assess outcomes related to the growth of fetal cardiac structures.

The efficacy of the clinical trial will be assessed by evaluating the impact of **materno-fetal hyperoxygenation (MFHO)** on the growth of underdeveloped fetal left ventricular structures during the third trimester of pregnancy. The primary endpoint for efficacy evaluation is the median change in the sum of the Z-scores of the initially chosen echocardiographic fetal heart structures under oxygen provocation. This will be measured at the time point PW35d0 (± 2 days) and compared to the initial values at PW32d0 (± 2 days) under the same conditions. The trial will utilize echocardiographic assessments to collect data on fetal heart structures, ensuring precise and reliable measurement of changes in cardiac development. The schedule for these assessments is clearly defined, with specific timepoints set for data collection to facilitate accurate analysis of the efficacy parameters. The trial is designed as a prospective, randomized, controlled, open, multicenter study, ensuring a robust evaluation of the treatment's efficacy.