PROTECT-AEGIS
A randomised feasibility comparison of ibuprofen after major gut surgery
Ibuprofen is a widely used and effective analgesic, but infrequently used after major gut surgery due to concerns about side effects, principally anastomotic breakdown. However, evidence to support withholding ibuprofen is weak. Many doctors and patients support a clinical trial to determine whether ibuprofen could be safely used for postoperative analgesia. This project will be co-led with Dr Caroline Thomas (Leeds/QMUL), with an award from NIHR-RfPb to part-fund this project.
Aim: To undertake a randomised feasibility comparison of postoperative ibuprofen plus usual postoperative analgesia after major gut surgery using the PROTECT platform.
Design and setting: Open-label randomised platform clinical trial with masked outcome assessment in 200 patients from 10 NHS hospitals.
Inclusion criteria:
- Patients aged 18 years and over undergoing major elective gut surgery with bowel anastomosis.
Exclusion criteria:
- Inability or refusal to provide informed consent
- Solid organ or bone marrow transplant
- Previous enrolment in the PROTECT-AEGIS trial
- Concomitant administration of any of the below:
- Another Non-Steroidal Anti-Inflammatory Drug
- Mifepristone within two weeks before surgery
- History of specific risk factors:
- Severe organ dysfunction defined as American Society of Anaesthesiologists (ASA) Physical Status Classification System 4 and/or eGFR <45
- Known hypersensitivity or allergic reaction to ibuprofen (or its excipients), or other Non-Steroidal Anti-inflammatory Drugs.*
- Peptic ulcer disease: two or more episodes of proven ulceration or bleeding, or upper gastrointestinal perforation
- Third trimester of pregnancy
- Solid organ or bone marrow transplant
Intervention: Oral ibuprofen 400mg three times daily for five days, started on postoperative day one, plus usual analgesic measures (epidural, Patient Controlled Analgesia, etc) and proton pump inhibitor (e.g. lansoprazole).
Comparator: Standard postoperative analgesic measures without NSAIDs.
Patient outcomes:
- Number of doses of ibuprofen or other NSAID administered to each patient within five days after surgery.
- Overall Benefit of Analgesia Scores (OBAS) recorded daily for five days after surgery
- Total opioid dose (Oral Morphine Equivalents) within five days after surgery.
- Numeric Rating Scale (NRS) pain scale on postoperative days one to five.
- All complications within 30 days of surgery.
- Mortality within 30 days of surgery.
- Duration of hospital stay within 30 days of surgery.
- Anastomotic leak graded within 30 days of surgery.
- Acute kidney injury (KDIGO creatinine definition only) within 30 days of surgery.
- Gastro-intestinal bleed within 30 days of surgery.
Hospital level feasibility outcomes:
- Number of eligible patients per year in each hospital.
- Number of eligible patients randomised per year in each hospital.
- Participating hospitals randomising at least one patient within the 12-month recruitment period.
- Number of consultant surgeons and anaesthetists in each hospital who support recruitment of the patients in their care in principle and the total number delivering care for elective colorectal surgery.