Trie Sur Baise, France

Study of Oral and Long-Acting Injectable Cabotegravir and Rilpivirine in Virologically Suppressed Children Living With HIV-1, Two to Less Than 12 Years of Age

This is a Phase I/II, multicenter, open-label, non-comparative study to evaluate the safety, tolerability, acceptability, and PK of oral CAB and oral RPV followed by long-acting injectable CAB (CAB LA) and long-acting injectable RPV (RPV LA) to propose the weight-band dosing in virologically suppressed children living with HIV-1 aged two to less than 12 years. The study will also assess the long-acting injectable regimen with and without an oral lead-in period in the same study population.

Friendship Bench Mental Health Intervention for Adolescent Girls and Young Women in South African PrEP Delivery Settings

This is a randomized hybrid implementation-effectiveness trial which will be conducted in a real-world healthcare setting. Eligible women who accept open-label daily oral PrEP (n=110) will be enrolled and randomized to either the Youth Friendship Bench SA intervention (plus standard-of-care mental health services as needed) or standard-of-care mental health services alone. Randomization will be conducted in a 1:1 ratio with randomly-sized blocks of ≤10. HIV-uninfected women ages 18-25 in Johannesburg, South Africa, who have symptoms of common mental disorders as evidenced by a score greater than or equal to 7 on the SRQ-20 will be eligible to enroll. The investigators hypothesize that the Youth Friendship Bench SA will significantly improve PrEP adherence and reduce symptoms of common mental disorders among AGYW at Month 3.

A Research Study on How Well Concizumab Works for You if You Have Haemophilia A or B With or Without Inhibitors

Staphylococcus Aureus Network Adaptive Platform Trial

Infection of the bloodstream with the bacterium Staphylococcus aureus (Staphylococcus aureus bacteraemia, SAB) is a serious infection that results in 15-30% of affected patients dying within three months of acquiring the infection. Treatment of this infection requires patients to be hospitalised, treated with prolonged antibiotics through an intravenous line, and carefully examined for the occurrence of complications associated with this condition. At present, there are many treatment options in current use, with no clear agreement as to which of these is best. The SNAP trial aims to identify which treatment options for SAB results in the fewest patients dying within the first 90 days after an infection. In contrast to a conventional clinical trial, the SNAP trial will examine multiple different treatment options at once. Patients will be randomly assigned to different concurrent treatment options currently considered acceptable in routine medical care, but as the trial progresses, more patients will be assigned to treatments that appear to have better outcomes than those with worse outcomes. The trial will adapt to accumulating trial evidence, on a regular basis, by removing treatment options found to be inferior, incorporating new treatment options, and ensuring that all patients in the trial receive the best treatments once they have been identified. Over time, we hope to determine the best combination of treatment options for patients with SAB. The SNAP Trial infrastructure will also support a number of sub-studies. A list of all active sub-studies can be found on the SNAP website: https://www.snaptrial.com.au/substudies.

Study of Adagloxad Simolenin (OBI-822)/OBI-821 in the Adjuvant Treatment of Patients With Globo H Positive TNBC

Safety and Tolerability of Metformin in People With Tuberculosis (TB) and Human Immunodeficiency Virus (HIV)

The METHOD trial is a Phase II A randomized, open-label trial of metformin added to standard anti-tuberculosis treatment (ATT) and anti-retroviral therapy (ART) in TB/HIV co-infected patients. HIV-positive adults (treated or ART-naïve) newly diagnosed with sputum culture-positive, drug-sensitive pulmonary TB will be recruited to and enrolled in the study. All participants in the interventional study will take standard ATT for drug-sensitive pulmonary TB starting at enrollment. Participants in the metformin arm will begin taking metformin 1 week later and metformin will be stopped on week-12. The "omics" control group will include those (treated or ART-naïve) without evidence of active TB. The total cohort is sample size N=112, comprising 56 participants each in two parallel study arms (standard therapy or standard therapy plus metformin) with the goal of retaining 100 participants with evaluable data for analysis. The duration of the METHOD trial is 5 years. The duration of individual participation in the interventional arms of the study is 36 weeks, not including an initial period of screening over an interval of up to 14 additional days prior to study enrollment. The final clinic visit coincides with the completion of ATT at week-24. The final follow-up contact is a phone interview at week-36. Ten consenting participants from each study arm (n=20 total) will have intensive pharmacokinetic/pharmacodynamic (PK/PD) sampling. The remaining 92 participants will have sparse PK/PD sampling.

A Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Participants With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer (lidERA Breast Cancer)

Characteristics of Young-onset Diabetes in Sub-Saharan Africa (YODA) Study

The specific objectives will be to; (1) characterise a population with clinically diagnosed type 1 diabetes and to determine the proportion of islet autoantibody positivity rates and to compare with a similar cohort of patients in the UK, (2) to determine the proportion of participants with retained endogenous insulin secretion (C-peptide > 600pmol/l) and whether they have evidence of autoimmunity as assessed by islet autoantibody and the type 1 diabetes genetic risk score Study setting: This study will be a multi-center cross-sectional study of clinically diagnosed type 1 diabetes patients who are currently on insulin treatment who are being followed-up in existing diabetes care centers in 4 sub-Saharan African countries; Cameroon, Uganda, Tanzania and South Africa. Recruitment will take place at regional diabetes care centers which usually serve as the main diabetes treatment hub for many smaller spoke clinics in the sub-region. In Cameroon, the Yaounde Central Hospital and the Bafoussam Regional Hospital will serve as main clinical sites. In Uganda the clinical sites involved are the Mulago National Referral and Teaching Hospital, St. Francis Hospital Nsambya, all in Kampala and the Masaka Regional Referral Hospital. The Muhimbili National Hospital in Dar Es Salaam will serve as the main clinical site in Tanzania. Cameroon, Uganda and Tanzania will carry out primary data collection over the study period while South Africa (University of Witwatersrand Medical School) will provide secondary data consisting of a minimal dataset and relevant collected samples for analysis. All these centers have existing diabetes care clinics with experienced staff who are used to collecting and providing data for research purposes. Eligibility: All patients with a clinical diagnosis of type 1 diabetes or young-onset insulin treated diabetes, who were diagnosed before the age of 30 years will be eligible to be enrolled into the study. We estimated a minimum total sample size of 500 participants will have a high precision with 95% confidence intervals of 17-25% around a prevalence of 20% for a clinical or biological characteristics (e.g. retained C-peptide or presence of islet auto-antibodies) and 46-54% around a prevalence of 50%. Sampling method: We will follow a systematic sampling method, enrolling consecutive eligible participants from the different primary collection clinical sites. Enrollment: All consented patients will be interviewed using a structured pre-tested questionnaire (Data Collection Form) by a trained study staff to collect relevant information; demographic, socioeconomic, lifestyle, family history, history of diabetes and diabetes complications. The questionnaire used in this study is available in English and has been translated into the major local language(s); the appropriate questionnaire is used according to the participant's preference. After the interview, a short clinical examination will be performed to record anthropometric characteristics (weight, height, waist and hip circumferences) and blood pressure. Using standardized operating procedures (SOPs), saliva, blood and urine samples will be collected from all study participants for biochemical analysis, and biobanking for future studies. Saliva will be used for DNA extraction and for the determination of type 1 genetic risk score (T1D GRS) using a 67 single nucleotide polymorphism score as described by Sharp et al. 2019. Venous whole blood will be used for full blood count and A1c determination. Plasma will be used for random C-peptide determination on the 801 module of the Cobas 8000 analyser and the measuring range will be truncated to <3pmol/L. Serum creatinine will be measured to assist in the interpretation of the C-peptide result. Islet autoantibodies, GAD, IA2 and ZnT8 will be measured in serum on the RSR Limited ELISA (RSR Limited, Cardiff, U.K.). Dipstick urinalysis will be done, with urinary C-peptide and creatinine measurement for the determination of the urinary C-peptide to creatinine ration (UCPCR). . Data collected from the different clinical sites using the data collection form will be entered into a centralized data management tool (REDCap). All data will be anonymised before being stored in the data management system. Ethical consideration: All participants will be required to provide a written informed consent before participating in the study. Refusal to participate will not affect the quality of care of the participants at the clinical sites. The study has received ethical clearance from the National Ethics Committee of Cameroon ( No 2018/12/1252/L/CNERSH/SP), and the Uganda Virus Research Institute (GC/127/19/12/736), Muhimbili National Hospital (MNH/IRB/I/2020/019) and Human Research Ethics Committe, South Africa (M200174).

Zimmer® Natural Nail® (ZNN) Bactiguard Tibia Post-Market Clinical Follow-up Study

This is a multicenter, prospective, Post-market Clinical Follow-up (PMCF) Study with retrospective controls. The study will enroll patients that will be implanted with the Zimmer Natural Nail Bactiguard Tibia device and retrospective controls implanted with standard titanium-alloy tibia nails. 500 tibias will be recruited at maximum 15 sites and allocated on a 1:1 ratio into an: - investigational group (prospective/consecutive series of 250 tibias treated with ZNN Bactiguard tibia) - a control group (retrospective series of 250 tibias treated with uncoated titanium-alloy tibia nail - data collection will be retrospective, these subjects will not have to undergo any study-related procedure). The primary endpoint is the Fracture Related Infection (FRI) rate in the study population 12 months after fracture fixation. The secondary endpoint is the confirmation of safety, performance and clinical benefits of ZNN Bactiguard implant and related instrumentation through the following measure systems: - Radiologic (RUST) & clinical (FIX-IT) fracture healing 12 months after fracture fixation (performance). - Patients' outcomes assessed by the Oxford Knee Score 12 months after fracture fixation (clinical benefits). - EQ5D-5L (patients' quality of life). - Incidence and frequency of adverse events (safety). Data will be collected at 2 weeks, 3 months, 6 months and 1 year after fracture fixation.

Transfusion Requirements in Younger Patients Undergoing Cardiac Surgery