Analgesic Effect of Parecoxib Versus Morphine in SCD Patients Presenting to the Emergency Department

Official title

Parecoxib Versus Morphine in Acute Pain Management for Sickle Cell Disease Patients in Emergency Department: a Randomized Controlled Trial.

Overview

Introduction: This study focuses on the treatment of painful crises in Sickle Cell Disease (SCD) patients using Paracoxib, a non-opioid, compared to Morphine. It addresses the need for alternative medications that reduce opioid dependency while providing effective analgesia. Objectives: Primary: Evaluate the analgesic effect of Paracoxib versus Morphine in SCD vaso-occlusive crises. Secondary: Reduce opioid use/dependence, decrease the length of hospital stays, and monitor side effects related to Paracoxib. Methodology: A double-blinded randomized controlled trial, conducted in a tertiary care emergency department. The study includes adult SCD patients with moderate to severe crises, excluding non-VOC pain, certain medications, and specific medical conditions. The sample size is 226 patients, split equally into two groups. Intervention: Patients receive either Morphine or Paracoxib, with periodic assessment of vital signs and pain. Additional Morphine is administered if required. Data collection and analysis are meticulously planned. Expected Outcomes: Improvement in SCD pain management, reduction in opioid usage, and potential benefits in terms of hospital stays and patient satisfaction.

Detailed description

Introduction: Sickle Cell Disease (SCD) is a prevalent hematological disorder in Oman. Patients frequently present to Emergency Departments (ED) with painful crises, often requiring high doses of opioids like Morphine. However, the complications associated with opioid use, including dependency, necessitate exploring alternative analgesic options. This research proposes a comparative study of Parecoxib, a non-steroidal anti-inflammatory drug (NSAID), and Morphine in managing pain for SCD patients in the ED.

Background: Recent studies have highlighted Parecoxib's potential in various clinical settings. In trauma patients, Parecoxib demonstrated comparable analgesic efficacy to Morphine, suggesting its broader applicability in the ED. Parecoxib has shown benefits in post-operative pain management, reducing opioid requirements and associated adverse events. Notably, in post knee replacement surgeries, Parecoxib effectively managed pain and facilitated functional recovery. It also contributed to decreased postoperative delirium in elderly patients undergoing hip or knee replacement surgery without increasing adverse events.

Research Objectives: The primary objective of this study is to evaluate the analgesic efficacy of Parecoxib versus Morphine in SCD patients experiencing vaso-occlusive crises. Secondary objectives include assessing the potential reduction in opioid dependence, length of hospital stay, recurrence of ED visits, and monitoring any Parecoxib-related side effects in SCD patients.

Methodology:

* Study Design: A double-blinded, randomized controlled trial. * Study Setting: AFH Emergency Department, a tertiary care institution. * Target Population: Adult SCD patients (\>18 years) presenting with moderate to severe vaso-occlusive crises. * Exclusion Criteria: Include non-VOC pain, weight \< 50 kg, frequent ED visits, recent opioid/NSAID use, contraindications to NSAIDs, lactating mothers, and recent visits to other health institutions. * Sample Size: The sample size of 226 patients, split into two groups of 113 each, was determined for a two-sided hypothesis test with a 5% significance level and 90% power. This design ensures a high probability of detecting a significant difference in the analgesic efficacy between Parecoxib and Morphine for SCD patients. The calculated size is based on expected effect sizes from previous research, with additional allowance for potential dropouts, ensuring the study's statistical validity and comprehensiveness. * Intervention: Computer-randomized administration of Morphine or Parecoxib. Continuous monitoring of vital signs and pain assessment at set intervals post-medication administration. Senior emergency physicians and residents will conduct assessments. * Data Collection and Analysis: The study will be double-blinded, with only the preparing nurse aware of the medication used. Data will be recorded using Epi-Data and analyzed using SPSS version 25.

Expected Outcomes: The study aims to enhance pain management protocols for SCD patients in the ED. By introducing Parecoxib as an alternative to opioids, we anticipate reduced opioid use, shortened hospital stays, fewer ED visits, and overall cost-effectiveness in managing SCD pain crises. The findings will be disseminated through local and international conferences and journals.

Interventions

• Drug Parecoxib
  Single dose of 40mg of IV Parecoxib.
• Drug Morphine
  Single dose of 5 mg of IV Morphine.

Primary outcome measures

• Pain reduction at 60 mins. [Time frame: 60 mintues]

Secondary outcome measures (3)

• Adverse Events/Side Effects [Time frame: 48 hours]
• The need of rescue pain medications [Time frame: 60 mintues]
• Recurrent visit [Time frame: 48 hours]

Eligibility criteria

Inclusion criteria

• An adult (>18 years) sickle cell disease patient presents with moderate-severe vaso-occlusive crisis (VOC) to the ED.

Exclusion criteria

• Non-VOC Pain (e.g. Acute chest syndrome, sequestration, septic arthritis, Etc.)
• Weight less than 50 KG
• Recurrent visits > one visit/ week
• Opioids within 24hrs
• NSAIDs within 24hrs
• Contraindications to NSAIDs (e.g. allergy, Asthma, CKD, pregnancy, Etc.)
• Lactating mothers
• Visited another health institution within 24hrs

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Baharuddin KA, Rahman NH, Wahab SF, Halim NA, Ahmad R. Intravenous parecoxib sodium as an analgesic alternative to morphine in acute trauma pain in the emergency department. Int J Emerg Med. 2014 Jan 3;7(1):2. doi: 10.1186/1865-1380-7-2. PMID 24386899
• Laoruengthana A, Rattanaprichavej P, Reosanguanwong K, Chinwatanawongwan B, Chompoonutprapa P, Pongpirul K. A randomized controlled trial comparing the efficacies of ketorolac and parecoxib for early pain management after total knee arthroplasty. Knee. 2020 Dec;27(6):1708-1714. doi: 10.1016/j.knee.2020.10.005. Epub 2020 Nov 13. PMID 33197808
• Stoltz RR, Harris SI, Kuss ME, LeComte D, Talwalker S, Dhadda S, Hubbard RC. Upper GI mucosal effects of parecoxib sodium in healthy elderly subjects. Am J Gastroenterol. 2002 Jan;97(1):65-71. doi: 10.1111/j.1572-0241.2002.05265.x. PMID 11808971
• Rasmussen GL, Steckner K, Hogue C, Torri S, Hubbard RC. Intravenous parecoxib sodium foracute pain after orthopedic knee surgery. Am J Orthop (Belle Mead NJ). 2002 Jun;31(6):336-43. PMID 12083587
• Zhuang Q, Tao L, Lin J, Jin J, Qian W, Bian Y, Li Y, Dong Y, Peng H, Li Y, Fan Y, Wang W, Feng B, Gao N, Sun T, Lin J, Zhang M, Yan S, Shen B, Pei F, Weng X. Postoperative intravenous parecoxib sodium followed by oral celecoxib post total knee arthroplasty in osteoarthritis patients (PIPFORCE): a multicentre, double-blind, randomised, placebo-controlled trial. BMJ Open. 2020 Jan 9;10(1):e030501. d PMID 31924632
• Mu DL, Zhang DZ, Wang DX, Wang G, Li CJ, Meng ZT, Li YW, Liu C, Li XY. Parecoxib Supplementation to Morphine Analgesia Decreases Incidence of Delirium in Elderly Patients After Hip or Knee Replacement Surgery: A Randomized Controlled Trial. Anesth Analg. 2017 Jun;124(6):1992-2000. doi: 10.1213/ANE.0000000000002095. PMID 28525512
• Nong L, Sun Y, Tian Y, Li H, Li H. Effects of parecoxib on morphine analgesia after gynecology tumor operation: a randomized trial of parecoxib used in postsurgical pain management. J Surg Res. 2013 Aug;183(2):821-6. doi: 10.1016/j.jss.2013.02.059. Epub 2013 Mar 30. PMID 23587455

Identifiers

NCT: NCT06315920 · AFMS-MREC 009/2021

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗