Trials (Sep 2021)

The PRolaCT studies — a study protocol for a combined randomised clinical trial and observational cohort study design in prolactinoma

  • Ingrid M. Zandbergen,
  • Amir H. Zamanipoor Najafabadi,
  • Iris C. M. Pelsma,
  • M. Elske van den Akker-van Marle,
  • Peter H. L. T. Bisschop,
  • H. D. Jeroen Boogaarts,
  • Arianne C. van Bon,
  • Bakhtyar Burhani,
  • Saskia le Cessie,
  • Olaf M. Dekkers,
  • Madeleine L. Drent,
  • Richard A. Feelders,
  • Johan P. de Graaf,
  • J. Hoogmoed,
  • Kitty K. Kapiteijn,
  • Melanie M. van der Klauw,
  • Willy-Anne C. M. Nieuwlaat,
  • Alberto M. Pereira,
  • Aline M. E. Stades,
  • Annenienke C. van de Ven,
  • Iris M. M. J. Wakelkamp,
  • Wouter R. van Furth,
  • Nienke R. Biermasz,
  • on behalf of the Dutch Prolactinoma Study Group

DOI
https://doi.org/10.1186/s13063-021-05604-y
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 13

Abstract

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Abstract Background First-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, although post-withdrawal remission rates are approximately 34%. Therefore, many patients require prolonged DA treatment, while side effects negatively impact health-related quality of life (HRQoL). Endoscopic transsphenoidal resection is reserved for patients with severe side effects, or with DA-resistant prolactinoma. Surgery has a good safety profile and high probability of remission and may thus deserve a more prominent place in prolactinoma treatment. The hypothesis for this study is that early or upfront surgical resection is superior to DA treatment both in terms of HRQoL and remission rate in patients with a non-invasive prolactinoma of limited size. Methods We present a combined randomised clinical trial and observational cohort study design, which comprises three unblinded randomised controlled trials (RCTs; PRolaCT-1, PRolaCT-2, PRolaCT-3), and an observational study arm (PRolaCT-O) that compare neurosurgical counselling, and potential subsequent endoscopic transsphenoidal adenoma resection, with current standard care. Patients with a non-invasive prolactinoma ( 2 years. PRolaCT-O will include patients who decline randomisation, due to e.g. a clear treatment preference. Primary outcomes are disease remission after 36 months and HRQoL after 12 months. Discussion Early or upfront surgical resection for patients with a limited-sized prolactinoma may be a reasonable alternative to the current standard practice of DA treatment, which we will investigate in three RCTs and an observational cohort study. Within the three RCTs, patients will be randomised between neurosurgical counselling and standard care. The observational study arm will recruit patients who refuse randomisation and have a pronounced treatment preference. PRolaCT will collect randomised and observational data, which may facilitate a more individually tailored practice of evidence-based medicine. Trial registration US National Library of Medicine registry (ClinicalTrials.gov) NCT04107480 . Registered on 27 September 2019, registered retrospectively (by 2 months).

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