Effectiveness of Endovascular Balloon Occlusion of the Aorta in Reducing Blood Loss During Cesarean Section in Patients with Placenta Accreta Spectrum Disorders in Tertiary Care Center in Kazakhstan: a Randomized Controlled Trial

Study design and study environment This will be a prospective, randomized controlled trial (RCT) that will investigate the superiority of REBOA in combination with cesarean section compared to the traditional cesarean section for pregnant women with PAD disorders. The study that will take place in the National Research Center for Mother and Children (NRCMC), University Medical Center (UMC), Astana, Kazakhstan. NRCMC is a tertiary care leading specialized institution in the field of obstetrics and gynecology in Kazakhstan. The hospital has sufficient experience in the field of scientific research, and a powerful technical and personnel base. Moreover, all UMC hospitals are part of Nazarbayev University Medical cluster (NU Medicine), which employs leading professors and researchers in the field of obstetrics and gynecology. The Center has a Department of Functional Diagnostics and Interventional Radiology with highly qualified specialists who have been trained at the international level. The NRCMC has all clinical units for patient admission and proper healthcare, 24/7 duty service of obstetricians-gynecologists and anesthesiologists-resuscitators. The diagnostic department has ultrasound machines with Doppler scanning opportunity (Philips, with a 9.4 Hz vaginal probe and a 5.1 Hz convex probe with Doppler) and magnetic resonance imaging machine (MRI), (PHILIPS Ingenia 3.0 T). The transfusiology department of NRCMC has a TEG5000 thromboelastograph device complete with a computer and a Haemonetics 2017 printer.

Study subjects The study population will consist of pregnant women who will be admitted to NRCMC of UMC for cesarean section due to placenta previa complicated by PAS disorders. Study subjects will be divided in cases and controls. The following inclusion criteria will be followed for case group: (1) singleton pregnancy at 34 weeks of gestation or more, (2) age 18 to 45 years, (3) confirmed diagnosis of placenta accreta spectrum, (4) indication for elective cesarean section, (5) consent for aortic balloon occlusion during cesarean section. Women who will not agree to undergo the aortic balloon occlusion procedure during cesarean section will be included in the control group.

The following exclusion criteria will be followed for both, case and control groups: (1) pregnant patients at the gestational age ˂ 34 weeks of gelation, (2) multiple pregnancy, (3) need for emergency caesarean section, (4) coagulopathy (known coagulopathy, women with abnormal baseline activated partial thromboplastin time (aPTT), prothrombin time (PT), international normalization ratio (INR) before surgery). In addition, patients on antiplatelet and anticoagulant drugs with known history of thrombotic events will be excluded.

Recruitment process The study participant recruitment will be performed from December 2024 to December 2025. Subjects who meet the eligibility criteria will be randomly assigned to either the intervention group (cesarean section + REBOA) or to traditional treatment group (control group) (cesarean section). A simple randomization method will be applied (Figure 1). Randomization will be based on a "single sequence of random assignments known as simple randomization" [27]. This technique maintains complete randomness of the assignment of a person to a particular group. The randomization procedure includes using a shuffled deck of cards (odd - intervention group, even - control group) [27]. The randomization will be performed after patients' recruitment, when the study aims and expected outcomes are disclosed to a patents and an informed consent is signed, by the responsible project team member.

Sample size calculation To estimate the required sample size, effect sizes for three major outcomes (mean intraoperative blood loss, blood transfusion volume, and hysterectomy rates) were derived from previous studies examining the impact of REBOA on reducing blood loss during cesarean sections in patients with placenta accreta spectrum disorders. Due to substantial heterogeneity in the effect sizes across studies (I2 for mean blood loss difference = 94.89% and I2 for mean transfusion volume = 86.95%), random-effects meta-analyses were conducted on individual study-level blood loss and transfusion volumes extracted from two previously published meta-analyses [28,29]. For hysterectomy outcome, a fixed-effect meta-analysis was applied due to lower heterogeneity (Q = 19.90, I2 = 29.64%).