Introduction

UK National Institute for Health and Care Excellence (NICE) recommends switch to oral antibiotics in neutropenic patients who are at low risk of complications after 48 hours of intravenous (IV) therapy. It noted that earlier oral switch may be beneficial for patients but must be further researched. EASI-SWITCH was randomized controlled trial (RCT) designed to address the evidence gap.

Aim

To determine if early switch to oral antibiotic treatment in adults with neutropenic sepsis at low risk of complications is non-inferior to switching late

Patient Profile

• N=125 participants from 16 centres were assessed
• Adults hospitalized patients presenting with neutropenic sepsis (NS) following systemic anti-cancer treatment (SACT) who were at low risk of complications
• Trial was terminated before reaching target sample size due to under-recruitment

Methods

• Non-inferiority, parallel-group, randomized, open-label clinical trial
• Randomization:
  • Standard Care arm (n=64): At least 48 hours IV antibiotics (meropenem or piperacillin-tazobactam). Then, oral switch and/or antibiotic discontinuation was at the physician's discretion
  • Intervention arm (n=61): 12 to 24 hours of IV antibiotics followed by switch to an oral regimen of ciprofloxacin 750 mg twice daily and co-amoxiclav 625 mg 3 times daily to complete 5 days' total treatment
• Follow-up: 28 days after randomization

Study endpoints

Primary: Composite measure of treatment failure, 14 days after randomization. Non-inferiority margin was 15%

Secondary: Time to resolution of fever from initial IV antibiotic administration; adverse events because of antibiotics or route of administration; length of hospitalization; and patient preferences for antibiotic treatment

Results

Primary Outcome

n=12 ITT patients excluded from the PP population

Intention To Treat (ITT) Analysis

• 14.1% in the standard care arm compared with 24.6% in the intervention arm met the primary end point. Risk difference 10.5% (1-sided 95% CI, −∞% to 22%; p 0.14)
• Intervention was not found to be non-inferior to standard care

Per-protocol population

• 13.3% in the standard care arm met the primary end point, compared with 17% in the intervention arm. Risk difference: 3.7% (one-sided 95% CI, −∞% to 14.8%; p 0.59)
• Intervention was found to be non-inferior to standard care

  A post hoc analysis found no statistically significant difference in risk of treatment failure, when accounting for possible clustering of observations within study sites. Risk difference:10.6 (95% CI, −3.2 to 54.4; p 0.13)

  Secondary Outcomes

• Duration of hospital stay was shorter in the intervention arm (median 2 [inter-quartile range (IQR) 2–3] vs. 3 days [IQR 2–4]; p 0.002)
• No statistically significant differences between trial arms for other measures

Adverse Events

Total of 29 serious adverse events were reported. Twelve serious adverse events occurred in the intervention arm

Patient Preference

Patients considered ‘important’ to be discharged 1 to 2 days earlier in intervention arm despite possible readmission risk increase

Conclusion

• Non-inferiority of early oral switch was found in the per-protocol population
• Intervention was not non-inferior in the intent-to-treat population possibly due to insufficient power arising from under-recruitment
• Trade-off between early switch, enabling early discharge, and the risk of treatment failure was acceptable to patients

Reference

Clin Microbiol Infect. 2024 Jan;30(1):92-99