CARE-CF-1 Clinical trial data: An exploratory, randomized, double-blind, placebo-controlled 6-arm clinical trial examining cysteamine as an adjunct therapy for the treatment of pulmonary exacerbations of cystic fibrosis

Background: Emerging data suggests a possible role for cysteamine as an
adjunct treatment for pulmonary exacerbations of cystic fibrosis (CF) that
continue to be a major clinical challenge. There are no studies
investigating the use of cysteamine in pulmonary exacerbations of CF. This
exploratory randomized clinical trial was conducted to answer the
question: In future pivotal trials of cysteamine as an adjunct treatment
in pulmonary exacerbations of CF, which candidate cysteamine dosing
regimens should be tested and which are the most appropriate, clinically
meaningful outcome measures to employ as endpoints? Methods and findings:
Multicentre double-blind randomized clinical trial. Adults experiencing a
pulmonary exacerbation of CF being treated with standard care that
included aminoglycoside therapy were randomized equally to a concomitant
14-day course of placebo, or one of 5 dosing regimens of cysteamine.
Outcomes were recorded on days 0, 7, 14 and 21 and included sputum
bacterial load and the patient reported outcome measures (PROMs): Chronic
Respiratory Infection Symptom Score (CRISS), the Cystic Fibrosis
Questionnaire–Revised (CFQ-R); FEV1, blood leukocyte count, and
inflammatory markers. Eighty nine participants in fifteen US and EU
centres were randomized, 78 completed the 14-day treatment period.
Cysteamine had no significant effect on sputum bacterial load, however
technical difficulties limited interpretation. The most consistent
findings were for cysteamine 450mg twice daily that had effects additional
to that observed with placebo, with improved symptoms, CRISS additional
9.85 points (95% CI 0.02, 19.7) p=0.05, reduced blood leukocyte count by
2.46x109 /l (95% CI 0.11, 4.80), p=0.041 and reduced CRP by geometric mean
2.57 nmol/l (95% CI 0.15, 0.99), p=0.049. Conclusion: In this exploratory
study cysteamine appeared to be safe and well-tolerated. Future pivotal
trials investigating the utility of cysteamine in pulmonary exacerbations
of CF need to include the cysteamine 450mg doses and CRISS and blood
leukocyte count as outcome measures.