Trial of prophylactic GCSF (white cell growth factor) use to prevent low white cell counts in people re-exposed to clozapine

Phase 2

• Conditions: eutropenia; Schizophrenia; Adverse drug reaction; Neutropenia; Blood - Other blood disorders; Mental Health - Schizophrenia

• Registration Number: ACTRN12618001830280
• Lead Sponsor: niversity of Queensland

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-11-09
• Last Update Posted: 11 November 2019

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1.Aged 18-64 years
2.Clinical diagnosis of schizophrenia according to DSM-V criteria
3.Treatment resistance defined as little or no symptomatic response to at least two antipsychotic trials of adequate duration (six weeks) and a previous trial of clozapine
4.Previously diagnosis of clozapine-associated neutropenia defined as absolute neutrophil count of <1.5 whilst prescribed a therapeutic dose of clozapine (50-900mg daily)
5.Considered by their treating psychiatrist to be likely to benefit from clozapine re-challenge or previously documented symptom response to clozapine which has not been maintained on alternative antipsychotic drugs
6.Ability to understand study risks and benefits, and to provide informed consent

Exclusion Criteria

1.Non-haematological contraindication to prescription of clozapine
2.Currently prescribed clozapine
3.Previous hypersensitivity reaction or allergy to G-CSF
4.Active haematological malignancy, active solid organ malignancy requiring cytotoxic or myelosuppressive therapy or cytotoxic exposure within one year of study screening
5.Existing or planned pregnancy or current breastfeeding
6.Absolute neutrophil count <2.0 at study entry
7.Homozygous sickle cell anaemia
8.Pre-existing moderate or severe thrombocytopenia (platelet count <100x109/L)
9.Pre-existing moderate or severe splenomegaly (craniocaudal diameter >150mm)
10.Active glomerulonephritis, aortitis and/or pulmonary haemorrhage

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Rate of recurrent neutropenia (absolute neutrophil count <1.5) assessed using regular complete blood examination assay. <br>Monitoring of complete blood examinations will occur weekly for the first 18 weeks of treatment and monthly thereafter if a stable ANC is achieved. If participants return an ANC of 1.5-2.0 or ANC >30 full blood count frequency will be increased to twice weekly until a stable ANC and filgrastim dosing regimen is achieved.[Cumulative rates at 12 months post-treatment.];Continued prescription of clozapine without haematological toxicity using data linkage to medical records and prescription records.[Cumulative rates at 12 months post-treatment.]

Secondary Outcome Measures

Name	Time	Method
Mean change in psychiatric symptom severity using positive, negative and total PANSS scores[18 weeks, 6 months, 12 months post-treatment.];Qualitative acceptability of filgrastim treatment using study specific questionnaire.[18 weeks, 6 months, 12 months post-treatment.];Side effect and safety profile using linkage to medical records, study specific questionnaire and symptom directed physical examination.<br>Common side effects of clozapine are weight gain, metabolic syndrome, diabetes, hypersalivation, nausea, severe constipation, tachycardia and nocturnal enuresis. Rare life-threatening adverse events include seizure, myocarditis, cardiomyopathy and venous or arterial thromboembolism.<br>Common side effects of filgrastim are bony pain and cytokine symptoms. Rare life-threatening adverse events include drug hypersensitivity reaction and splenic rupture.[Weekly for the first 18 weeks then at 6 months and 12 months post-treatment.]