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.

In low-income and middle-income countries, significant geographical and socioeconomic inequalities affect access to eye care. This study explores an equity-focused approach to improve access to eye care services provided by a community-based eye care organisation in northern India.

A sequential exploratory mixed-method approach.

A high-volume eye screening programme in north Indian villages. Individuals identified with eye care needs during the screening were referred to the six nearby primary eye care centres.

7578 individuals identified with eye needs through a community-based eye screening programme. Of these, 4431 (58.6%) were women and 3137 (41.4%) were men.

Socioeconomic questions, developed by experts and lay representatives, were integrated into an ongoing digitally supported (Peek Vision) eye screening programme in north Indian villages. Data from referred individuals identified with eye needs were analysed using logistic regression with a mixed-effect model to identify socioeconomic characteristics most strongly associated with poor access to care after referral. A sequential exploratory mixed-method approach, including in-person interviews and follow-up telephonic surveys of individuals with these characteristics, was used.

To identify barriers and gather suggestions for improving attendance from groups least likely to attend services.

Of 7627 individuals referred for eye care, 7578 (99.3%) participated in the study. Of those, 2937 (38.5%) attended the Vision Centre, to which they were referred. The least likely to attend were individuals aged >16, those with dependents, and those referred for non-cataract conditions. Among the 3939 individuals with all three characteristics, the attendance rate was 35.3% compared with 42.5% (p

Suggested programme improvements, including better counselling, reminder calls and transportation, could increase access among those least likely to access services after referral. This study demonstrates a two-step approach for identifying solutions from individuals facing the most significant barriers to care. We will go on to conduct trials of these suggested interventions.