European Sickle Cell Disease Cohort – Hydroxyurea – Extension study (ESCORT-HU Extension)

Study type

• Study topic:
  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Other
• If ‘other’, further details on the scope of the study:
  Safety study (non comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  SIKLOS
• Study drug International non-proprietary name (INN) or common name:
  HYDROXYCARBAMIDE
• Anatomical Therapeutic Chemical (ATC) code:
  (L01XX05) hydroxycarbamide

  hydroxycarbamide
• Medical condition to be studied:
  Sickle cell disease
• Additional medical condition(s):
  SCD

Population studied

• Short description of the study population:
  Male or female patients, aged ≥ 2 years old, with symptomatic sickle cell disease, treated with Siklos.
• Age groups:
  • Paediatric Population (< 18 years)

    • Preterm newborn infants (0 – 27 days)
    • Term newborn infants (0 – 27 days)
    • Infants and toddlers (28 days – 23 months)
    • Children (2 to < 12 years)
    • Adolescents (12 to < 18 years)
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  2100

Study design details

• Study design:
  Multicentre, prospective, non-interventional cohort study
• Main study objective:
  The primary objective of the study is to determine the long-term safety profile of Siklos® focusing on risks which are poorly documented or unknown (unknown meaning: nature and frequency of serious adverse events causally related to Siklos® which are not listed in the product information).
• Setting:
  Investigators will be recruited among physicians experienced in sickle cell disease (SCD) management. Participants will be followed for up to 5 years. The study started in August 2020 and will be completed in August 2025.;
• Outcomes:
  The primary endpoint is the occurrence of malignancies, leg ulcers, male fertility impairment (oligospermia, azoospermia) and serious unexpected AEs (meaning SAEs which are not listed in the product information) according to the causal relationship with Siklos® or not and main features of these events.; ; Secondary endpoints are :; • Mean age at first periods for females, mean age of puberty for males and contraception,; • Incidence of the use of cryopreservation for the purpose of paternity, management of semen cryopreservation and semen analysis,; • Management of Siklos® during pregnancy and outcome of pregnancy following exposure at the time of conception or at any time during the pregnancy,; • Frequency and reason for temporary (>15 days) or permanent discontinuations of Siklos®, ; • Switch or combination with alternative treatment,; • Complications linked to SCD at enrolment and occurring during follow-up,; • Quality of life for adults patients
• Data analysis plan:
  The analyses will be mainly descriptive and no formal statistical testing will be carried out.
• Summary results:
  A total of 2050 patients were enrolled in the study at the time of this final analysis. Among those, 2045 patients (99.8%) fulfilled the criteria for inclusion in the Safety Population. 55.6% patients of the Safety Population were females and 44.4% were males. ; Median exposure duration to HU was 10 years. ; During ESCORT-HU Extension study follow-up, ; • 27 patients (1.3%) had a malignancy diagnosed after the start of the study. ; • 128 patients (6.3%) developed leg ulcer(s) (202 events); 10 were related to HU. ; • 19 patients had semen analysis. Among those, 15 patients were diagnosed with male fertility impairment: 2 qualitative abnormalities, 12 quantitative abnormalities and 3 patients with both qualitative and quantitative abnormalities. ; • 4 patients experienced a SUSAR (acute spleen sequestration, hypogonadism, retinal micro bleeding, type 2 diabetes). ; • 138 pregnancies were reported in 111 female patients: 69 pregnancies were with normal birth (50.7%) and 17 with premature birth (12.5%). Forty-two (42) pregnancies (30.9%) were reported without living child, 6 were ongoing, data was missing for 2 pregnancies and 2 had unknown outcome. Among those, Siklos® treatment had not been interrupted before conception in 28 cases. ; • 34 pregnancies were reported in 30 male patients: 27 with normal birth (88.2%), 3 (8.8%) without living child, and 1 (2.9%) pregnancy was ongoing. Among those, Siklos® treatment had not been interrupted before conception in 17 cases.