Outpatient paracentesis for the management of ovarian hyperstimulation syndrome: study protocol for the STOP-OHSS randomised controlled trial.

INTRODUCTION: Ovarian hyperstimulation syndrome (OHSS) is the most significant short-term complication of pharmacological ovarian stimulation. Symptoms range from mild abdominal discomfort to rare complications such as renal failure, thromboembolism and respiratory distress syndrome.Currently, clinical practice typically involves monitoring the patient until the condition becomes severe, at which point they are admitted to hospital, where drainage of ascitic fluid (paracentesis) may take place. Preliminary studies have indicated that earlier outpatient paracentesis may reduce the progression of OHSS and prevent hospitalisation in women. METHODS AND ANALYSIS: This UK, multicentre, pragmatic, two-arm, parallel-group, adaptive (group sequential with one interim analysis), open-label, superiority, confirmatory, group sequential, individually randomised controlled trial, with internal pilot will assess the clinical and cost-effectiveness and safety of outpatient paracentesis versus conservative management (usual care) for moderate or severe OHSS. 224 women from 20 National Health Service and private fertility units will be randomised (1:1) and followed up for up to 13.5 months. The primary outcome is the rate of OHSS related hospital admission of at least 24 hours within 28 days postrandomisation. The primary analysis will be an intention to treat with difference in hospitalisation rates as measure of treatment effect. Secondary outcomes include time to resolution of symptoms, patient satisfaction, adverse events and cost-effectiveness. A qualitative substudy will facilitate the feasibility of recruitment. Participant recruitment commenced in June 2022. ETHICS AND DISSEMINATION: London-Southeast Research Ethics Committee approved the protocol (reference: 22/LO/0015). Findings will be submitted to peer-reviewed journals and abstracts to relevant national and international conferences, as well as being disseminated to trial participants and patient groups. TRIAL REGISTRATION NUMBER: ISRCTN71978064.

Study protocol for the Multiple Symptoms Study 3: a pragmatic, randomised controlled trial of a clinic for patients with persistent (medically unexplained) physical symptoms.

INTRODUCTION: Persistent physical symptoms (which cannot be adequately attributed to physical disease) affect around 1 million people (2% of adults) in the UK. They affect patients' quality of life and account for at least one third of referrals from General Practitioners (GPs) to specialists. These referrals give patients little benefit but have a real cost to health services time and diagnostic resources. The symptoms clinic has been designed to help people make sense of persistent physical symptoms (especially if medical tests have been negative) and to reduce the impact of symptoms on daily life. METHODS AND ANALYSIS: This pragmatic, multicentre, randomised controlled trial will assess the clinical and cost-effectiveness of the symptoms clinic intervention plus usual care compared with usual care alone. Patients were identified through GP searches and mail-outs and recruited by the central research team. 354 participants were recruited and individually randomised (1:1). The primary outcome is the self-reported Physical Health Questionnaire-15 at 52 weeks postrandomisation. Secondary outcome measures include the EuroQol 5 dimension 5 level and healthcare resource use. Outcome measures will also be collected at 13 and 26 weeks postrandomisation. A process evaluation will be conducted including consultation content analysis and interviews with participants and key stakeholders. ETHICS AND DISSEMINATION: Ethics approval has been obtained via Greater Manchester Central Research Ethics Committee (Reference 18/NW/0422). The results of the trial will be submitted for publication in peer-reviewed journals, presented at relevant conferences and disseminated to trial participants and patient interest groups. TRIAL REGISTRATION NUMBER: ISRCTN57050216.