Phase III Trial for Venous Thromboembolism

Case Study

Background:
PPD was awarded a Phase III trial by a large pharmaceutical company to test the safety and efficacy of a highly selective, orally administered inhibitor of coagulation factor Xa for the prophylaxis of venous thromboembolism in acutely ill patients. This study included more than 6,500 subjects across 372 sites in 35 countries.

Objective:
The primary objective was to demonstrate that oral administration of the investigational product for 30 days reduces the rate of total venous thromboembolism (VTE) and VTE-related death compared to standard, subcutaneous administration of the current product for a minimum period of six days in subjects with acute medical illness.

Challenges:
Complexity of the study introduced challenges from recruitment through data management:

• Older patient population (over 40)
• VTE prophylaxis not standard of care in some regions, especially in non-surgical patients
• 30 exclusion criteria, including specific lab cutoffs often seen in the target patient population
• High prescreen failure rate
• Hybrid study with paper process for serious adverse event queries
• Significantly higher than expected serious adverse events and query rates

Strategy:
Careful and creative planning was required to overcome several challenges and meet the client’s timeline and quality needs:

• Added sites in Peru and Colombia and doubled the number of sites in India to meet recruitment goals
• Modified the on-site visit schedule, replacing some visits with telephone contact to improve visit compliance
• Created study-specific electronic case report form (eCRF) completion guidelines to clarify data entry expectations
• Implemented a global summary tracker to highlight at-risk sites and provide a single tracker used as a communication tool with the client

Results:

• Delivered results on schedule, meeting deadlines for database lock and last patient in
• Conducted 11,000 compression ultrasounds with all but five being submitted by the deadline
• Client praised the pharmacovigilance team’s ability to manage and track the adjudication process and to proactively identify, manage and escalate potential issues