What are the TIME and AMPLE trials for pleural effusion management?

TIME and AMPLE Trials for Pleural Effusion Management

Overview of the Trials

The TIME-2 and AMPLE trials were landmark randomized controlled trials comparing indwelling pleural catheters (IPCs) versus talc pleurodesis for managing malignant pleural effusions with expandable lung. 1

TIME-2 Trial Key Findings

The TIME-2 (Therapeutic Intervention in Malignant Effusion) trial demonstrated:

• No significant difference in dyspnea improvement between IPCs and talc pleurodesis at 42 days 1
• Both interventions resulted in improved dyspnea scores from baseline, but the Visual Analog Score improvement between groups at 6 months showed no clinically meaningful difference 1
• IPCs were associated with fewer days spent in hospital during patients' remaining life 1
• IPCs had lower treatment failure rates (defined as need for additional interventions) 1
• IPCs carried higher risk of cellulitis compared to talc pleurodesis 1

AMPLE Trial Key Findings

The AMPLE (Australian Malignant Pleural Effusion) trial corroborated TIME-2 findings:

• No difference in dyspnea improvement at 30 days between IPCs and chemical pleurodesis 1
• Similar patterns of hospital length of stay reduction with IPCs 1
• Confirmed the increased cellulitis risk with IPC placement 1

Clinical Impact on Guidelines

These trials fundamentally changed malignant pleural effusion management by establishing that:

Either IPCs or chemical pleurodesis can be used as first-line definitive intervention for symptomatic malignant pleural effusions with expandable lung 1, 2, 3

This represented a major shift, as previous guidelines had restricted IPCs primarily to patients with nonexpandable lung 1

Decision-Making Algorithm Based on Trial Evidence

Choose IPC when:

• Minimizing hospital time is the priority (IPCs reduce total hospitalization days) 1
• Patient has limited life expectancy and wants outpatient management 2
• Risk of treatment failure needs to be minimized 1
• Patient can manage catheter care at home 3

Choose Talc Pleurodesis when:

• Avoiding infection risk is paramount (lower cellulitis rates than IPCs) 1
• Patient cannot manage catheter care 3
• Patient preference is for single definitive procedure 1

Critical Caveats from These Trials

The trials specifically enrolled patients with expandable lung - this is essential because pleurodesis requires visceral and parietal pleura in apposition 1

At least 30% of malignant pleural effusion patients have nonexpandable lung, making them unsuitable for pleurodesis and requiring IPC as the only viable option 1, 3

Cellulitis risk with IPCs, though ranked below critical outcomes like dyspnea relief, was significant enough to result in a neutral recommendation rather than favoring one intervention over the other 1

Subsequent Evidence

The IPC-Plus study (published after TIME-2 and AMPLE) showed that combining IPC with talc slurry resulted in higher pleurodesis rates and improved quality of life compared to IPC with saline alone 1, suggesting combination therapy may offer advantages over either approach alone.