Pre-eclampsia and fetal growth restriction are leading causes of perinatal morbidity and mortality. A therapy that enhances maternal vascular function and promotes vasodilation to increase placental perfusion could treat both conditions.

Tissue kallikrein-1 is an endogenous enzyme that releases bradykinin to activate the bradykinin 2 receptor on endothelial cells. This induces potent vasodilation and pro-angiogenic, anti-oxidant and anti-inflammatory effects.

DM199 is a recombinant form of tissue kallikrein which can be administered intravenously or subcutaneously. Clinical trials in non-pregnant populations have demonstrated its safety. Being a protein, it is unlikely to cross the placenta. This protocol describes an early-phase trial for DM199 for pre-eclampsia and fetal growth restriction.

This phase IB/IIA open-label trial at Tygerberg Hospital, Western Cape Province, South Africa, will determine the safety and effective dose of DM199 for pre-eclampsia and/or fetal growth restriction. The trial consists of two parts. Part 1 will be an ascending dose finding study, treating women with pre-eclampsia and severe hypertension who are for planned birth within 72 hours. This will search for doses that safely lower blood pressure (n=3/dose, recruiting up to 42 participants). Part 2 is a safety and efficacy study of three cohorts of pregnant women (n=30/cohort): (1) with pre-eclampsia and severe hypertension requiring delivery within 72 hours, (2) with preterm pre-eclampsia (

The trial has ethical approval (Health Research Ethics Committee, Stellenbosch University, Protocol number M24/04/009) and is registered (Pan African Clinical Trial Registry, PACTR202404895013782) and approved by the South African Health Products Regulatory Authority (20240801). Data will be presented at international conferences and published in peer-reviewed journals.

Due to nursing shortages, an ageing population and increasing care demand, there is a growing interest in parenteral medication administration at home (PMAaH), comprising the administration of parenteral medication in the home situation of patients. The operational design of such PMAaH care pathways is complex, resulting in many variations of adoptions, showing a need for a quality framework. Although quality indicators (QIs) have been proposed to monitor the quality of specific care pathways, a generic quality framework for all types of PMAaH is lacking. Therefore, this study proposes a generic quality set for PMAaH, which includes structure and process QIs, to benchmark and redesign PMAaH care pathways to ensure high quality.

A generic QI set was developed for PMAaH using a systematic RAND appropriateness method adapted at the third phase. This method consisted of a scoping review to identify indicators, an expert panel rating phase including an online questionnaire and subsequent panel meeting to assess the appropriateness of the indicators and a retrospective practice testing to evaluate the feasibility, clarity and measurability of the indicators. After the practice testing, which consisted of an online questionnaire where experts could indicate the implementation state of all indicators in their hospital, a third expert panel adjusted the set to increase the likelihood of implementation in practice.

The experts, all healthcare professionals involved in PMAaH processes, were recruited using the snowball sampling technique from three large Dutch, teaching hospitals. Subsequently, a practice testing by self-assessment was conducted in seven large Dutch teaching hospitals.

17 and seven healthcare professionals with diverse backgrounds participated in the online questionnaire and panel meeting, respectively.

The scoping review resulted in 36 QIs for PMAaH. After two expert panel rating rounds (online questionnaire and panel meeting), two indicators were removed: a QI related to travel distance policy since it was irrelevant and redundant, and a QI stating that a clinician should take the lead in a PMAaH-team, which was deemed too restrictive. After the practice testing, two QIs were removed: a QI related to clinical response documentation, which was unclear for the practice testing respondents and already covered by other QIs, and a QI related to survival documentation, which was deemed infeasible and undesirable to measure this differently than other patients by the third expert panel.

The final set consists of 32 indicators (of which 15 were structure indicators and 17 were process indicators). The final set predominately includes QIs that are aimed at patient safety but also QIs focusing on the working conditions of the healthcare workers. 17.6% of the QIs are currently fully implemented in general in all seven hospitals. The practice testing revealed that operational QIs are more frequently implemented in practice than systemic QIs and that a structured quality assurance programme is needed in the hospitals.

This study proposes a generic quality set for PMAaH that hospitals can use to redesign and benchmark PMAaH care pathways to assure high quality. The practice testing confirmed that there is a need for this structured quality set.