Role of Antibiotic Therapy or Immunoglobulin On iNfections in hAematoLogy Platform Trial (RATIONAL-PT)

(IVIg) intravenous immunoglobulin every 4 weeks ± 1 week at a dose of 0.4g/kg, modified to achieve an (IgG) immunoglobulin G trough level of at least lower limit of age-specific serum IgG reference range; or SCIg, weekly, may be used in patients who meet local criteria for home-based self-administration in centres with established SCIg programs. Dosing is usually given at 100mg/kg/week, modified to achieve an IgG steady state level of at least the lower limit of the serum reference range. A loading IVIg dose may be given in the first month if required.

Once daily trimethoprim-sulfamethoxazole (co-trimoxazole) 160mg/800mg. Doxycycline 100mg daily as an alternative for patients with hypersensitivity to co-trimoxazole.

Patients will be provided with amoxycillin/clavulanic acid 1750-2000mg/250mg and ciprofloxacin 750 mg to keep at home for initial use if symptoms of infection develop, with immediate review by their treating clinical team, or nearest emergency department or medical practitioner with phone contact to treating team if most practical. Clindamycin 600 mg is permitted as an alternative to amoxycillin/clavulanic acid for patients with hypersensitivity to penicillin. Ciprofloxacin is omitted for participants with hypersensitivity.

Arm A: Low dose (IgRT) immunoglobulin replacement therapy: Participants will be treated with intravenous immunoglobulin monthly (every 4 weeks ± 1 week) at a dose of 0.25g/kg. No dose adjustment for trough serum IgG levels is required. Arm B: Usual dose: Participants will be treated with intravenous immunoglobulin monthly (every 4 weeks ± 1 week) at a dose of 0.4g/kg, modified to achieve an IgG trough level of at least lower limit of age-specific serum IgG reference range.