Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Comparing Acute Pain Management Protocols for Patients With Sickle Cell Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02222246
Recruitment Status : Completed
First Posted : August 21, 2014
Results First Posted : August 4, 2017
Last Update Posted : August 4, 2017
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
University of Cincinnati
Mount Sinai Hospital, New York
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date  ICMJE August 19, 2014
First Posted Date  ICMJE August 21, 2014
Results First Submitted Date  ICMJE May 12, 2017
Results First Posted Date  ICMJE August 4, 2017
Last Update Posted Date August 4, 2017
Actual Study Start Date  ICMJE March 15, 2015
Actual Primary Completion Date May 31, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 31, 2017)
Difference in Pain Score as Measured by a Visual Analogue Scale (VAS) [ Time Frame: Arrival in ED to discharge from the ED, up to 6 hours ]
Each ED study visit was the unit of analysis for the statistical methods addressing the primary outcome. The primary outcome was change in pain score from arrival to discharge. Pain severity was assessed at arrival and discharge from ED using a 100 mm visual analogue scale (VAS). The VAS range is 0 to 100 with 0 indicating "no pain" and 100 indicating "pain as bad as it could be" or "worst imaginable pain".Discharge was defined by which one of the following occurred first: (a) decision to admit to hospital; (b) patient physically leaves the ED to home; or (c) after six hours of observation in the ED. Thus, the difference in pain scores were calculated as the arrival minus discharge VAS scores, with higher positive pain difference or change scores indicating greater pain reduction.
Original Primary Outcome Measures  ICMJE
 (submitted: August 19, 2014)
Difference in Pain Score as Measured by a Visual Analogue Scale (VAS) [ Time Frame: Arrival in ED to discharge from the ED, up to 6 hours ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2017)
  • Change in Pain Visual Analogue Scale (VAS) Scores Over Time [ Time Frame: Every 30 minutes from arrival in ED to discharge from the ED, up to 6 hours ]
    Pain severity was assessed at arrival and every 30 minutes until discharge from the ED using a 100 mm visual analogue scale (VAS). The VAS range is 0 to 100 with 0 indicating "no pain" and 100 indicating "pain as bad as it could be" or "worst imaginable pain". Discharge was defined by which one of the following occurred first: (a) decision to admit to hospital; (b) patient physically leaves the ED to home; or (c) after six hours of observation in the ED. A hierarchical random coefficients regression model for repeated measurements (type of mixed hierarchical mixed-effect model) was conducted on the pain scores collected at six time points (arrival, post-placement 30-min, 60-min, 90-min,120-min, discharge) to evaluate the trajectory of change in pain. Discharge occurred at 120 minutes or later during each visit, with the exception of one discharge at 54 minutes.
  • Incidence of Nausea During Emergency Department Visits [ Time Frame: From placement in Emergency Department (ED) treatment room to discharge from the ED, up to 6 hours ]
    Nausea at any point from placement until discharge, based on nausea data collected every 30 minutes during that time period. Thus, a nausea variable was derived in which 0=no and 1=yes that nausea was reported by the patient at least once during the placement to discharge time interval.
  • Incidence of Vomiting During Emergency Department Visits [ Time Frame: From placement in ED treatment room to discharge from the ED, up to 6 hours ]
    Vomiting at any point from placement until discharge, based on vomiting data collected every 30 minutes during that time period. Thus, a vomiting variable was derived in which 0=no and 1=yes that vomiting was reported by the patient at least once during the placement to discharge time interval.
  • Incidence of a Decrease in Systolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit [ Time Frame: From placement in ED treatment room to discharge from the ED, up to 6 hours ]
    Decrease in systolic blood pressure at any point from placement until discharge, based on blood pressure data collected every 30 minutes during that time period. A systolic variable was derived in which 0=no and 1=yes that a >= 20% decrease of baseline systolic blood pressure was reported by the patient at least once during the placement to discharge time interval.
  • Incidence of a Decrease in Diastolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit [ Time Frame: From placement in ED treatment room to discharge from the ED, up to 6 hours ]
    Decrease in diastolic blood pressure at any point from placement until discharge, based on blood pressure data collected every 30 minutes during that time period. A diastolic variable was derived in which 0=no and 1=yes that a > 20% decrease of baseline diastolic blood pressure was reported by the patient at least once during the placement to discharge time interval.
  • Incidence of Oxygen Desaturation (< 95%) (YES) During Emergency Department Visit [ Time Frame: From placement in ED treatment room to discharge from the ED, up to 6 hours ]
    Saturation of peripheral capillary oxygen < 95% (SPO2 < 95%) at any point from placement until discharge, based on SPO2 data collected every 30 minutes during that time period. Thus, a SPO2 variable was derived in which 0=no and 1=yes that SPO2 < 95% was reported by the patient at least once during the placement to discharge time interval.
  • Incidence of Respiratory Distress (YES) During Emergency Department Visit [ Time Frame: From placement in ED treatment room to discharge from the ED, up to 6 hours ]
    Respiratory distress at any point from placement until discharge, based on data collected every 30 minutes during that time period. Thus, a respiratory distress variable was derived in which 0=no and 1=yes that respiratory distress was reported by the patient at least once during the placement to discharge time interval.
  • Incidence of Sedation During Emergency Department Visit [ Time Frame: From placement in ED treatment room to discharge from the ED, up to 6 hours ]
    Severe-to moderate sedation at any point from placement until discharge, based on sedation data collected every 30 minutes during that time period. Thus, a sedation variable was derived in which 0=no and 1=yes that moderate-severe sedation was reported by the patient at least once during the placement to discharge time interval. Sedations scoring was as follows: None was defined as "awake and alert", Mild sedation was defined as "responds to voice", Moderate sedation was defined as "responds to touch, with or without voice" and Severe sedation was defined as "somnolent, difficult to arouse".
  • Incidence of the Need for Supplemental Oxygen During Emergency Department Visit [ Time Frame: Following the initiation of opioid therapy until discharge from the ED, up to 6 hours ]
    Need for supplemental oxygen during the Emergency Department stay; this was determined at discharge.
  • Incidence of the Administration of Naloxone During Emergency Department Visit [ Time Frame: Following the initiation of opioid therapy until discharge from the ED, up to 6 hours ]
    Naloxone administered during the Emergency Department stay; this was determined at discharge.
  • Incidence of the Need for Assistive Ventilation [ Time Frame: Following the initiation of opioid therapy until discharge from the ED, up to 6 hours ]
    Intubation or other assistive ventilation techniques - including bag, valve, or mask was performed during the ED stay; this was determined at discharge.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 19, 2014)
  • Change in Pain Visual Analogue Scale (VAS) scores over time [ Time Frame: Every 30 minutes from arrival in ED to discharge from the ED, up to 6 hours ]
  • Incidence of nausea [ Time Frame: Every 30 minutes from placement in ED treatment room to discharge from the ED, up to 6 hours ]
    Study staff will ask patients whether they are experiencing any nausea (yes/no).
  • Incidence of vomiting [ Time Frame: Every 30 minutes from placement in ED treatment room to discharge from the ED, up to 6 hours ]
    Study staff will ask patients whether they have vomited since the last study assessment (yes/no).
  • Incidence of a decrease in BP (> 20% of baseline BP) [ Time Frame: Every 30 minutes from placement in ED treatment room to discharge from the ED, up to 6 hours ]
    Study staff will measure blood pressure (BP), and notify ED staff of a decrease in BP from patient's arrival in the ED of 20% or more.
  • Incidence of oxygen desaturation (< 95% from baseline) [ Time Frame: Every 30 minutes from placement in ED treatment room to discharge from the ED, up to 6 hours ]
    Study staff will measure oxygen saturation (SpO2) via a pulse oximeter, and notify ED staff of SpO2 readings less than 95% from baseline.
  • Incidence of respiratory depression [ Time Frame: Every 30 minutes from placement in ED treatment room to discharge from the ED, up to 6 hours ]
    Study staff will measure respiratory rate (RR),and notify ED staff of RR < 10 breaths per minute.
  • Incidence of sedation [ Time Frame: Every 30 minutes from placement in ED treatment room to discharge from the ED, up to 6 hours ]
    Study staff will access the level of a patient's self-reported sedation using a scale ranging from 1 (least sedated) to 4 (most sedated), and notify ED staff of a score of 4.
  • Incidence of the need for supplemental oxygen [ Time Frame: Every 30 minutes following initiation of opiod therapy until discharge from the ED, up to 6 hours ]
    Study staff will note the patient's need for supplemental oxygen via the use of a nasal cannula (yes/no).
  • Incidence of the administration of naloxone [ Time Frame: Following the initiation of opiod therapy until discharge from the ED, up to 6 hours ]
    A patient's need for naloxone administration.
  • Incidence of the Need for Assistive Ventilation [ Time Frame: Following the initiation of opiod therapy until discharge from the ED, up to 6 hours ]
    A patient's need for intubation or other assistive ventilation technique including bag, valve, and mask.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Comparing Acute Pain Management Protocols for Patients With Sickle Cell Disease
Official Title  ICMJE Comparing Acute Pain Management Protocols for Patients With Sickle Cell Disease
Brief Summary The goal of this pilot study is to improve emergency department (ED) pain management for adults with sickle cell disease. Sickle cell disease (SCD) is the most common genetic disorder in the United States, and occurs primarily among African Americans. Management of painful episodes associated with SCD, referred to as vaso-occlusive crises (VOC), is the most common reason for SCD patients to visit the ED. Currently, there is no standard approach to managing VOC pain in the ED that is widely accepted and used, and pain management for vaso-occlusive crisis in persons with SCD is very different between providers and not based on research. Many times, patients who come to the ED with sickle cell pain feel that they do not receive adequate pain control. If EDs could provide efficient, effective, safe, patient-centered analgesic management, it may be possible to improve pain management for adults with SCD experiencing a VOC. Guidelines for treating vaso-occlusive crises caused by sickle cell disease will soon be published by the National Heart, Lung and Blood Institute of the National Institutes of Health. These guidelines recommend patient-specific pain treatment protocols or a standardized pain management protocol for SCD when a patient does not already have a pain treatment protocol designed for them. The purpose of this pilot study is to compare these two ways to treat vaso-occlusive pain in the ED for adults with sickle cell disease, and to determine if a large randomized controlled trial is feasible and required.
Detailed Description

In August 2012 the National Heart, Lung, and Blood Institute (NHBLI) released for public comment their "Management of Sickle Cell Disease" evidence-based recommendations that were developed with consensus panel expertise. Because of a lack of empirical data, most of the recommendations specific to vaso-occlusive crises (VOC) were based on consensus panel expertise. Recommendations included the use of a patient-specific protocol (specific agents and doses for an individual patient). While many attempts have been made to implement patient-specific analgesic protocols for use in emergency departments (EDs), anecdotally, these have been difficult to implement and maintain over time; a practical approach to development, implementation, and dissemination has not been determined. As patient-specific protocols are not available in most EDs, the guidelines go on to recommend a SCD specific standard analgesic protocol. Both of these recommended protocols provide more aggressive VOC pain management than a typical generic ED pain protocol. However, there is an urgent need to rigorously test the NHLBI recommendations and compare the two approaches for managing VOC in the ED. A large randomized clinical trial (RCT) is essential to test these protocols.

This pilot project will compare these two different, evidence-based, protocols which include opioid pain medicines routinely used as standard of care to treat VOC pain in the ED for individuals with SCD, and collect the data necessary to determine if a large RCT is feasible and required. This study is novel in that it will design an approach to develop and implement patient-specific and standard analgesic VOC protocols for use in the ED, will develop a bundle of information technology and education interventions to enhance protocol adoption for the pilot RCT, and also be the first RCT conducted in an ED setting to compare two different ED pain management protocols for SCD patients who experience a VOC.

The study consists of 3 aims:

  1. Develop and implement patient specific VOC protocols for patients randomized to this arm,
  2. Conduct a pilot RCT to determine the necessary sample size needed for a large RCT to compare the difference in reduction in pain score from ED arrival to discharge, hospitalization, clinical and safety outcomes, between subjects assigned randomly to either a standard SCD analgesic protocol or to a patient-specific analgesic protocol,
  3. Measure feasibility of methods and acceptability of and fidelity to protocols by evaluating optimal recruitment and retention strategies, and assessing ED providers perceptions of facilitators and barriers to protocol use and protocol adherence.

The soon to be published NHBLI guidelines for managing SCD will be used as the standard protocol with the modification of basing the initial dose of pain medicine on patient weight. The standard protocol will recommend re-assessment, and re-dosing with possible dose escalation, every 20-30 minutes. Repeat doses for patients randomized to the weight-based protocol, when necessary, will be maintained or provided at 1 dose level increase (no more than 25%) above the initial dose. For patients randomized to the patient -specific protocol, the SCD provider has experience with the individual patient and is best qualified to make dosing and frequency recommendations based upon doses required during past ED and hospital visits for treatment of VOC, and on daily opioid use if applicable. There is no set maximum dose for patients randomized to the patient-specific protocols.

Both the patient-specific and standard protocols will be available in the ED via a patient's electronic medical record. Upon ED arrival, providers will retrieve the patient's study protocol (patient-specific, or standard) which will include the starting agents, and doses, the subsequent analgesic recommendations, and order medications according to the pre-determined protocol.

The study will be conducted at the emergency departments of the University of Cincinnati Medical Center and the Mt. Sinai Hospital in New York. Patients will be enrolled in the study for up to 12-months, but may contribute no more that five different ED visits for VOC pain control during enrollment to allow for a larger number of different patients.

Study outcomes will be compared between ED visits of patients randomized to a patient-specific vs. a standard SCD protocol. The primary outcome will be the difference in pain score from ED arrival to discharge, up to 6 hours, as measured using a visual analogue scale. The trajectories of average pain scores from immediately prior to administration of 1st analgesic dose to discharge by 30 minute increments for each treatment group will also be calculated.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE
  • Drug: Hydromorphone (Standardized, weight-based dosing)
    Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).
    Other Name: Dilaudid
  • Drug: Morphine Sulfate (Standardized, weight-based dosing)
    Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).
  • Drug: Hydromorphone (Patient Specific dosing)
    Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.
    Other Name: Dilaudid
  • Drug: Morphine Sulfate (Patient Specific dosing)
    Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.
Study Arms  ICMJE
  • Experimental: Patient Specific dose of Morphine Sulfate or Hydromorphone
    A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 5 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.
    Interventions:
    • Drug: Hydromorphone (Patient Specific dosing)
    • Drug: Morphine Sulfate (Patient Specific dosing)
  • Active Comparator: Standard dose of Morphine Sulfate or Hydromorphone
    A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.
    Interventions:
    • Drug: Hydromorphone (Standardized, weight-based dosing)
    • Drug: Morphine Sulfate (Standardized, weight-based dosing)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 8, 2016)
106
Original Estimated Enrollment  ICMJE
 (submitted: August 19, 2014)
77
Actual Study Completion Date  ICMJE June 30, 2016
Actual Primary Completion Date May 31, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult SCD patients with genotypes SS, SC, SB+, or SB-

Exclusion Criteria:

  • Patients with sickle cell trait
  • Allergic to both morphine sulfate and hydromorphone,
  • Patients who have an explicit care plan that states they cannot be admitted to the hospital for pain control,
  • Non-English speaking,
  • Patients admitted for a medical complication,
  • Record of >24 ED visits in the prior 12 months,
  • Children
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02222246
Other Study ID Numbers  ICMJE Pro00054047
R34 RHL121224A ( Other Grant/Funding Number: NHLBI )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Duke University
Study Sponsor  ICMJE Duke University
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • National Heart, Lung, and Blood Institute (NHLBI)
  • University of Cincinnati
  • Mount Sinai Hospital, New York
Investigators  ICMJE
Principal Investigator: Paula Tanabe, PhD Duke University School of Nursing
PRS Account Duke University
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP