Ibuprofen and Opioid (Morphine or Diamorphine) for Acute Pain in Sickle Cell Disease - Sickle With Ibuprofen & Morphine (SWIM)

An Evaluation of the Effectiveness of Ibuprofen and Opioid (Morphine or Diamorphine) for Acute Pain in Sickle Cell Disease: a Double-blind, Placebo-controlled Randomised Trial

The use of oral ibuprofen combined with Opioid (Morphine or Diamorphine) administered through patient controlled analgesia (PCA) will be clinically effective for acute pain crisis in adults with sickle cell disease (SCD).

Study Overview

• Status: Terminated
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Ibuprofen; Drug: Diamorphine or Morphine; Drug: Placebo

Detailed Description

Pain from vaso-occlusion in sickle cell disease (SCD) is persistent, and its management continues to pose a challenge to practitioners. Opioids are recommended for the treatment of severe acute SCD pain, and have been used successfully within the hospital setting. Non-steroidal Anti-Inflammatory Drugs (NSAIDs) are recommended for acute SCD pain, however there is no clear evidence for the effectiveness of oral NSAIDs in combination with parenteral opioids in adults with SCD.Data from acute pain research suggests that oral ibuprofen is one of the best NSAIDs for combination treatment with morphine via PCA.

This is a randomised controlled trail to evaluate the effectiveness of oral ibuprofen plus intravenous Diamorphine or morphine via PCA. The results will provide the evidence needed to recommend whether or not ibuprofen should be used in acute SCD pain.

• Study Type: Interventional
• Enrollment (Anticipated): 320
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom, NW10 7NS
    • North West London Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients with SCD of any phenotype

Exclusion Criteria:

• Patient has a history of allergic reaction to either diamorphine/morphine or ibuprofen
• Patient has contraindications to diamorphine/morphine or ibuprofen, e.g. peptic ulcer disease, non-steroidal anti-inflammatory drug (NSAID)-induced asthma
• Patient in a drug dependency programme
• Patient is on renal dialysis
• Stroke within the last 6 weeks
• Platelet count less than 50 x 10^9/l
• Patient is pregnant or breastfeeding
• Doctor unwilling to randomise the patient for other reasons
• Previous participation in the trial
• Patient receiving drug treatment with which opioids or NSAIDs are likely to interact significantly
• Stage 1 - 5 chronic kidney disease (ref Appendix 2), including urine protein: creatinine ratio of >50 (Because the ibuprofen dose is substantial it is felt that precautions should be taken to exclude those who have any signs of chronic kidney disease. One of the signs of kidney disease is "persistent proteinuria". Therefore, the patient who intermittently has proteinuria(which could be due to other reasons) could still participate.)
• Oxygen saturation by pulse oximetry <94%
• Participation in another clinical trial within the last month

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Diamorphine or Morphine by PCA and oral ibuprofen	Drug: Ibuprofen; Oral ibuprofen 800 mg three times daily for a total of 2400 mg per day for 4 days; Drug: Diamorphine or Morphine; Diamorphine or Morphine by PCA
Placebo Comparator: 2; Diamorphine or Morphine by PCA and oral placebo	Drug: Diamorphine or Morphine; Diamorphine or Morphine by PCA; Drug: Placebo; Matching placebo three times daily for 4 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Patient controlled analgesia (PCA)diamorphine or morphine consumption	4 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Rapidity of pain control - time to achieve a pain score of 4 on a standard 10-point numeric rating scale	4 days

Collaborators and Investigators

• Sponsor: London North West Healthcare NHS Trust
• Collaborators: Medical Research Council CTU
• Investigators: Principal Investigator: Kofi A Anie, PhD, London North West Healthcare NHS Trust; Study Chair: Gavin Cho, MD, London North West Healthcare NHS Trust; Principal Investigator: Mark Layton, MD, Imperial College London; Study Director: Sarah Meredith, MD, MRC Clinical Trials Unit; Study Director: Caroline Dore, BSc, MRC Clinical Trials Unit

Publications and helpful links

General Publications

• Cho G, Anie KA, Buckton J, Kiilu P, Layton M, Alexander L, Hemmaway C, Sutton D, Amos C, Dore CJ, Kahan B, Meredith S. SWIM (sickle with ibuprofen and morphine) randomised controlled trial fails to recruit: lessons learnt. BMJ Open. 2016 Jun 9;6(6):e011276. doi: 10.1136/bmjopen-2016-011276.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Anticipated): March 1, 2014
• Study Completion (Anticipated): August 1, 2014

Study Registration Dates

• First Submitted: April 9, 2009
• First Submitted That Met QC Criteria: April 10, 2009
• First Posted (Estimate): April 13, 2009

Study Record Updates

• Last Update Posted (Estimate): December 4, 2012
• Last Update Submitted That Met QC Criteria: December 3, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Pain; Morphine; Patient Controlled Analgesia; Sickle Cell Disease; Ibuprofen; Diamorphine
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Acute Pain; Anemia, Sickle Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Analgesics, Opioid; Narcotics; Morphine; Ibuprofen; Heroin
• Other Study ID Numbers: HTA 07/48/01; ISRCTN97241637