Blantyre, Malawi

A Study of Belrestotug Plus Dostarlimab Compared With Placebo Plus Pembrolizumab in Previously Untreated Participants With Programmed Death Ligand 1 (PD-L1) High Non-small-cell Lung Cancer (NSCLC)

Safety and Efficacy of Anakinra Treatment for Patients With Post Acute Covid Syndrome

People with COVID-19 might have sustained post-infection sequelae, known as Post-Acute Covid Syndrome (PACS). A recent consensus definition by an international panel of 265 patients, clinicians, researchers, and WHO staff suggests that post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, and cognitive dysfunction and generally have an impact on everyday functioning. The role of immune dysregulation in PACS is indirectly supported from the findings of the SAVE-MORE randomized clinical trial, in which patients with moderate and severe COVID-19, were 1:2 randomized to treatment with placebo or anakinra once daily for 10 days. The primary endpoint was the distribution of the frequencies of patients in the 11 points of the WHO clinical progression scale (CPS) by day 28. Patients' follow-up until day 90 showed significant reduction of the incidence of PACS; this was 24.4% among placebo-treated patients and 15.7% among patients treated with anakinra. After the end of the SAVE-MORE trial, the understanding of the immune activation of PACS and the development of tools for the evaluation of patients have become the main aims of the Hellenic Institute for the study of sepsis (HISS) group. More precisely, patients with medical history of COVID-19 pneumonia during three separate time periods and matched comparators for age, sex, comorbidities, and state of vaccination were followed up and evaluated for PACS. Main findings can be summarized as follows: 1. For at least one year after acute COVID-19 there is considerable immune dysregulation involving both the innate and the adaptive responses. 2. Patients with PACS may be classified into four main phenotype clusters: fatigue involving 70.8%, respiratory cluster involving 33.2%, systemic symptoms involving 17.7% and other symptoms involving 26.1%. 3. The risk for progression into PACS was significantly lower among patients treated with anakinra in the acute stage (odds ratio 0.59, p: 0.017) showing a role of IL-1 for the progression into PACS. 4. Patients with fatigue bring distinct immunotype compared to the respiratory cluster. 5. IP-10 (interferon-gamma-induced protein-10) at levels more than 250 pg/ml has sensitivity 99.3%, specificity 90.9%, positive predictive value (PPV) 97.9% and negative predictive value (NPV) 97.6% for the diagnosis of the post acute COVID immune dysregulation. PRECISION is a proof-of-concept, randomized clinical trial (RCT) aiming to evaluate the efficacy and safety of anakinra in patients with PACS in improving the clinical and immunological state over 4 to 8 weeks as measured by a composite endpoint, namely, the "Score of PACS progression reversal".

Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients with Homozygous Familial Hypercholesterolemia

This is a multicenter, international, long-term observational study investigating the real-world impact of lomitapide on Major Adverse Cardiovascular Events (MACE) in patients with Homozygous Familial Hypercholesterolemia (HoFH). Study Design: Observational, open-label, retrospective and prospective study Data will be collected from >26 lipid centers across Europe Patients will serve as their own control, with comparisons between pre-treatment (3 years before lomitapide) and post-treatment (first 3 years of lomitapide therapy) periods Study Population: Approximately 72 adult patients (≥18 years) diagnosed with HoFH Patients must have received lomitapide for at least 12 months Availability of 3 years of pre-treatment clinical records Objectives: Primary Objective: Evaluate the incidence of MACE before and after lomitapide treatment Secondary Objectives: Assess changes in LDL-C, total cholesterol, liver function tests (ALT, AST, GGT), and lipid-lowering therapy usage (e.g., discontinuation of LDL apheresis, addition of PCSK9 inhibitors) Endpoints: Primary Endpoint: Change in MACE incidence over the 3-year treatment period Secondary Endpoints: Changes in lipid levels, liver safety markers, and adherence to treatment protocols Safety Considerations: The study follows real-world clinical practice, with monitoring of adverse events, including liver-related safety concerns associated with lomitapide Data will be collected in an electronic Case Report Form (eCRF) and analyzed following Good Clinical Practice (GCP) guidelines This study aims to generate real-world evidence on the cardiovascular impact of lomitapide in HoFH patients, addressing an unmet clinical need for data on long-term outcomes.

An Investigator-Initiated, Phase II, Multicenter, Open-Label, Single-Arm, Prospective Clinical Trial to Evaluate the Efficacy and Safety of Alternating Bortezomib-Based Regimens in Combination With DaratUMumab Followed by Maintenance With Daratumumab in the Frontline Setting of Primary Plasma CEll L

This is an investigator-initiated, prospective, multicenter, phase II, open-label, single-arm, non-randomized, single-stage clinical trial. The study comprises the following phases: A 28-day screening phase An induction phase which includes six 21-day induction treatment cycles of alternating D-PAD and D-CVD (starting with D-PAD) Note: Based on the post-induction treatment disease evaluation, transplant-eligible subjects who have achieved ≥SD and PBPC ≤2% will undergo ASCT whereas those with SD or PBPC 2% will discontinue study treatment. Accordingly, transplant-eligible subjects who have achieved ≥PR will receive 2 additional D-CVD cycles whereas those with <PR will discontinue study treatment. ASCT (single or tandem) (applicable for transplant-eligible patients) A consolidation phase which includes two 21-day consolidation cycles of D-CVD A maintenance phase which includes twenty-four 28-day cycles of daratumumab monotherapy (applicable for subjects who have achieved ≥PR at the end of consolidation phase [Cycle 8]) An End of Treatment (EOT) visit: 30 days (±7 days) after the last dose of all components of the study treatment have been discontinued A Post-Treatment Follow-Up (PTFU) phase which will begin once a subject permanently discontinues study treatment. In particular: All subjects who complete or discontinue study treatment without disease progression (PD), will return to the site every 12 weeks (±2 weeks) for disease evaluation (or sooner at Investigator's discretion if there are concerns for progression/relapse) and other follow-up assessments until the earliest of confirmed PD, start of subsequent therapy for PCL, death, or the end of study (EOS) definition is met. After confirmed PD or the start of a new anticancer treatment for PCL, subjects will return to the site or be contacted by telephone every 16 weeks (±2 weeks) for collection of follow-up information (i.e., other malignancies, next-line therapy, and survival, as applicable) until death, withdrawal of consent for study participation, or the EOS definition is met, whichever occurs first.

Fast Antibiotic Susceptibility Testing for Gram Negative Bacteremia Trial

Assessing the Procalcitonin-guidance and Molecular-guided Diagnosis for Therapy of Severe Infections (the MODIFY Trial)

Early administration of antimicrobials remains the mainstay of treatment of severe infections. The time until start of antimicrobials is so crucial that every hour of delay impacts considerably on mortality. In everyday clinical practice even when antimicrobials are administered early, it is impossible to know whether they are appropriate or not because cultures of specimens collected from the patient require at least 48 to 72 hours to provide some information about the type of pathogen and the antimicrobial susceptibilities. BioFire ® FilmArray ® possesses four Food and Drug Administration (FDA)-cleared panels of molecular diagnosis, capable of detecting multiple targets in less than an hour of sample handling. Among them, Blood Culture Identification 2 Panel (BCID2) covers 43 targets. BCID2 provides information on the genes of resistance to antibiotics the microorganisms carry. BCID2 combined with fast AST can, however, introduce revolutionary changes in minimizing the time until the appropriate antimicrobial is prescribed. The concept of Reveal is to provide AST for a full panel of antibiotics if one Gram-negative isolate is identified in the blood flask. Evaluation of the appropriateness of the administered therapy and decision about discontinuation or de-escalation of antimicrobials, is based on the use of biomarkers and mainly procalcitonin (PCT).

ARTEMIS - A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With a Heart Attack

Safety and Pharmacokinetics of FBR-002 for the Treatment of Patients Hospitalized With COVID-19 in Need of Supplemental Oxygen and at Risk of Severe Outcome

LOWER: Lomitapide Observational Worldwide Evaluation Registry

To evaluate the occurrence of adverse events of special interest, long term effectiveness of lomitapide, and to evaluate whether prescribers of lomitapide are following screening and monitoring recommendations as specified in product labeling.