Refractory haEmorrhage Devices trial: Efficacy of uterine tamponade devices for management of refractory postpartum haemorrhage

Stage 1 • Three uterine tamponade devices (Ellavi® free-flow, Ellavi® fixed-volume, or Suction Tube Uterine Tamponade (STUT)) will be evaluated. Arm 1: Ellavi® fixed-volume The Ellavi® balloon, is a fully pre-assembled UBT device made of plastic that can be quickly filled up to 750 mL without expansion pressure. Arm 2: Ellavi® free-flow Although most purpose-designed UBTs work as fixed-volume systems, the Ellavi® balloon can also work with a free-flow mechanism, through an open gravidity-fed system. Arm 3: STUT The STUT device consists of a FG36 Levin stomach tube connected to suction apparatus or to an MVA device. It is an improvised device that uses vacuum force to collapse the uterus by mimicking physiologic uterine contractions. Procedure Women admitted to hospital in early labour will be informed about the trial and will be asked to provide informed consent. All women will receive a uterotonic drug for PPH prophylaxis and a plastic drape will be placed under their buttocks to measure ongoing postpartum blood loss as part of local standard practice. In cases of atonic PPH, treatment will be provided according to local policies including uterotonics, tranexamic acid and IV fluids. If bleeding cessation is not achieved at the judgement of the attending physician and she/he considers that further treatment is required, a research midwife will immediately randomize the consenting woman to one of the trial interventions. The physician in charge will insert the allocated device into the uterine cavity. The balloon is then inflated, or suction is switched on. The physician re-evaluates the bleeding every 5 minutes for the next quarter of an hour; if bleeding does not stop within 15 minutes, the device is removed and further treatment is provided according to local policies; if bleeding has stopped, the device stays in place for the next 6 hours without further action. After 6 hours the device will be removed; if bleeding resumes the device will be kept in place until 24 hours, when it will be definitely removed. All participants will receive prophylactic antibiotics according to local policies. Selection of the best performing device At the end of Stage I, an interim analysis will be conducted to identify the best performing device, based on the observed decrease in the incidence of the primary outcome. In case more than one device showed a positive effect on the composite primary outcome, compared with the control, the device with the most favourable profile in terms of acceptability and adherence to the protocol will be selected for stage 2. In case the effect size was larger than expected, the trial might be stopped early for loss of clinical equipoise. If none of the research devices showed a potential reduction of the primary outcome by at least 33% compared with the control arm, the trial would be stopped early for futility. Stage 2 The best performing device identified in Stage 1 will progress to Stage 2 where it will be compared directly to the control device. Outcomes and procedures will be the same at both stages. This stage would start at the same hospitals three months after the completion of Stage 1. More hospitals and countries could join the study for Stage 2.