A critical analysis of an early terminated clinical trial with an antifungal new dosing regimen for children and adults with Cystic Fibrosis and Aspergillus

  • Reema Alhwij

Student thesis: Master typesMaster en sciences biomédicales à finalité spécialisée en recherche clinique


Background: Invasive fungal disease is still a major cause of morbidity and mortality in immunocompromised and, to a lesser degree, immunocompetent patients. Current therapies are unsatisfactory. Posaconazole is an extended range triazole having antifungal efficacy against Aspergillus species in vitro and in vivo. This open- label study’s objectives were to prospectively verify a new Posaconazole dose regimen and clinically evaluate Posaconazole's usage to treat
Aspergillus infection in children with cystic fibrosis. Unfortunately, the sponsor decided to terminate the study because they will not be able to complete recruitment within reasonable timelines.
Aim: The trial was terminated early due to limited patient enrolment and the advent of a new medicine on the market during the study's duration. The primary goal of this master thesis is to conduct a critical analysis of the current study, to identify what the pitfalls were and to determine the reasons that led tothe study's early termination.
Methods: To examine the clinical effectiveness of Posaconazole and to support the study's concept, studies from PubMed and clinical trials.gov were searched. Google questionnaire and CVBF site were used to examine the elements that contributed to the study's early termination.
Results and conclusion: Posaconazole is used as an off label and effective medication for cystic fibrosis, according to the literature analysis. Large RCT trials should be conducted to validate this hypothesis. In this open-label trial, 1500 patients were expected to be included, with 135 of them to be enrolled into the intervention phase following a positive sputum culture. Finally only 29
patients were screened, and only one patient was enrolled for the intervention phase, which was randomly assigned to the control group. Patients were unable to produce sputum, resulting in a poor patient recruitment rate. The more, all sites have deviated from the protocol in various ways. According to the questionnaire, COVID-19 pandemic situation had no effect on the trial
execution and investigators preferred to prescribe the new drug that became available on the market. Many factors contributed to the study's early termination and these factors will be published as it may help in the success of other trials.
la date de réponse16 sept. 2022
langue originaleAnglais
L'institution diplômante
  • Universite de Namur
SuperviseurYves Geysels (Promoteur)

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