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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Ibuprofen
* Drug: Placebo
* Drug: Diamorphine or Morphine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Disease, Pain, Ibuprofen, Morphine, Diamorphine, Patient Controlled Analgesia