The PRolaCT studies — a study protocol for a combined randomised clinical trial and observational cohort study design in prolactinoma
Trials, vol. 22, pp. 653
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 (< 25 mm) will be eligible for one of three RCTs based on the duration of pre-treatment with DAs: PRolaCT-1: newly diagnosed, treatment-naïve patients; PRolaCT-2: patients with limited duration of DA treatment (4-6 months); and PRolaCT-3: patients with persisting prolactinoma after DA treatment for > 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).
Authors 23
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Ingrid Marijke Zandbergen corresponding Aachen Department of Medicine Center for Endocrine Tumours Leiden Division of Endocrinology, Leiden University Medical Center Department of Neurosurgery, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Medicine, Center for Endocrine Tumours Leiden, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands. prolactinoom@lumc.nl
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands. prolactinoom@lumc.nl
Department of Neurosurgery, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands. prolactinoom@lumc.nl
Department of Neurosurgery, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
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Amir H. Zamanipoor Najafabadi Aachen Department of Medicine Center for Endocrine Tumours Leiden Department of Neurosurgery, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Medicine, Center for Endocrine Tumours Leiden, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Department of Neurosurgery, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
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Iris C. M. Pelsma Aachen Department of Medicine Center for Endocrine Tumours Leiden Division of Endocrinology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Medicine, Center for Endocrine Tumours Leiden, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
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M. Elske van den Akker‐van Marle Aachen Department of Biomedical Data Sciences Section Medical Decision Making
Leiden University Medical Center
Affiliation as printed
Department of Biomedical Data Sciences, Section Medical Decision Making, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
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Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers
Affiliation as printed
Department of Medicine, Division of Endocrinology, Amsterdam University Medical Center - location AMC, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands
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Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Department of Neurosurgery, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands
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Affiliation as printed
Department of Internal Medicine, Rijnstate, Wagnerlaan 55, 6815AD, Arnhem, The Netherlands
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Elisabeth-TweeSteden Ziekenhuis
Affiliation as printed
Department of Neurosurgery, Elisabeth-Tweesteden Ziekenhuis, Hilvarenbeekseweg 60, 5022GC, Tilburg, The Netherlands
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Saskia le Cessie Aachen Department of Biomedical Data Sciences Section Medical Decision Making Department of Clinical Epidemiology
Leiden University Medical Center
Affiliation as printed
Department of Biomedical Data Sciences, Section Medical Decision Making, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Department of Clinical Epidemiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
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Olaf M. Dekkers Aachen Department of Clinical Epidemiology Department of Medicine Division of Endocrinology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Clinical Epidemiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
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Amsterdam University Medical Centers · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Medicine, Division of Endocrinology, Amsterdam University Medical Center - location VUmc, De Boelelaan 1118, 1081HZ, Amsterdam, The Netherlands
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Affiliation as printed
Department of Medicine, Division of Endocrinology, Erasmus Medical Center, Doctor Molewaterplein 40, 3015GD, Rotterdam, The Netherlands
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Affiliation as printed
Dutch Pituitary Foundation, PO BOX 1014, 3860BA, Nijkerk, The Netherlands
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Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers
Affiliation as printed
Department of Neurosurgery, Amsterdam University Medical Center - location AMC, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands
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Affiliation as printed
Department of Gynaecology, Reinier de Graaf Gasthuis, Reinier de Graafweg 5, 2625AD, Delft, The Netherlands
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University Medical Center Groningen
Affiliation as printed
Department of Medicine, Division of Endocrinology, University Medical Center Groningen, Hanzeplein 1, 9713GZ, Groningen, The Netherlands
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Elisabeth-TweeSteden Ziekenhuis
Affiliation as printed
Department of Internal Medicine, Elisabeth-Tweesteden Ziekenhuis, Hilvarenbeekseweg 60, 5022 GC, Tilburg, The Netherlands
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Alberto M. Pereira Aachen Department of Medicine Center for Endocrine Tumours Leiden Division of Endocrinology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Medicine, Center for Endocrine Tumours Leiden, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
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University Medical Center Utrecht
Affiliation as printed
Department of Medicine, Division of Endocrinology, University Medical Center Utrecht, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands
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Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Department of Medicine, Division of Endocrinology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, The Netherlands
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Affiliation as printed
Department of Internal Medicine, St. Antonius Ziekenhuis, Koekoekslaan 1, 3435CM, Nieuwegein, The Netherlands
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Wouter R. van Furth Aachen Department of Medicine Center for Endocrine Tumours Leiden Department of Neurosurgery, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Medicine, Center for Endocrine Tumours Leiden, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Department of Neurosurgery, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
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Nienke Ruurdje Biermasz Aachen Department of Medicine Center for Endocrine Tumours Leiden Division of Endocrinology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Medicine, Center for Endocrine Tumours Leiden, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands
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