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THE IMPROVE TRIAL: Improving Pain Management and Outcomes With Various Strategies of Patient-Controlled Analgesia (PCA) (IMPROVE)

Primary Purpose

Sickle Cell Disease

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
High Demand / Low Infusion
PCA Dosing Plan
Sponsored by
Carelon Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Sickle Cell Disease: Hemoglobin diagnosis of SS (two copies of the hemoglobin S gene), SC (one copy of the hemoglobin S gene and one copy of the hemoglobin C gene), SD (one copy of the hemoglobin S gene and one copy of the hemoglobin D gene), or S-β thalassemia (β+ or β0)
  • Male or female age ≥ 10 years.
  • Typical vaso-occlusive pain that is not adequately controlled in an ambulatory or acute care setting and which is expected to require > 24 hours of hospital care.
  • Pain Intensity Visual Analog (10 cm scale) score ≥ 4.5 cm, measured immediately after obtaining informed consent.
  • Adults willing and able to give informed consent; parents willing and able to give permission for study participation by their children; minor subjects (ages 10-17) willing and able to provide assent.
  • Ability to read/write English.

Exclusion Criteria:

  • Medical Indication

    • Presence of significant liver disease (ALT > 3 times institutional upper limit of normal, or direct bilirubin > 0.8 mg/dl within preceding 3 months)
    • Presence of significant renal dysfunction (within preceding 3 months, creatinine ≥ 1.2 mg/dl for ages >18 yrs, or ages 10-18 yrs creatinine ≥ 1.0 mg/dl)
    • Oxygen saturation by pulse oximetry ≤ 92% on room air at study entry
    • Any other medical condition that renders the subject unable to or unlikely to complete the study or which would interfere with optimal participation in the study or which poses significant risk to the subject from study treatment including but not limited to:
    • Concurrent acute chest syndrome
    • Right upper quadrant pain
    • Symptomatic sleep apnea
    • Brain injury or doses of opioids that preclude potential subjects' capacity to give informed consent.
  • Known (documented) hypersensitivity/intolerance to morphine and/or hydromorphone.

  • Clinically significant opioid tolerance in the opinion of the investigator that precludes safe and/or effective dosing or requires, under current management, receiving the following long-acting oral opioids:

    • Methadone 40 mg/day
    • Sustained/Extended release oral morphine 120 mg /day
    • Oxycodone 80 mg/day
  • Known pregnancy or currently breastfeeding.
  • Poor venous access that in the investigator's judgment would preclude maintaining an IV throughout the admission.
  • Currently participating in another research study.
  • Previously randomized in the IMPROVE trial.
  • Pain management in emergency department or Day Hospital ≥ 12 hours prior to decision to admit for inpatient care.
  • Subject or physician preference for treatment with opioids other than morphine or hydromorphone.

Sites / Locations

  • Children's Hospital and Research Center
  • Yale-New Haven Medical Center,
  • A.I. duPont Hospital for Children
  • Children's National Medical Center
  • Howard University Hospital
  • Emory University School of Medicine
  • Medical College of Georgia
  • Children's Memorial Hospital
  • University of Illinois Sickle Cell Center
  • Kosair Children's Hospital
  • Children's Hospital at Sinai
  • Johns Hopkins
  • National Institutes of Health Clinical Center
  • Boston Medical Center
  • Children's Hospital Boston
  • University of Mississippi Medical Center
  • Interfaith Medical Center
  • New York Methodist Hospital
  • The University of North Carolina at Chapel Hill
  • Duke University Medical Center
  • Cincinnati Children's Hospital Medical Center
  • Nationwide Children's Hospital
  • Ohio State University
  • Children's Hospital of Philadelphia
  • St. Christopher's Hospital for Children
  • Children's Hospital of Pittsburgh
  • Texas Children's Hospital
  • Virginia Commonwealth University Health Systems

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

High Demand / Low Infusion

Low Demand / High Infusion

Arm Description

PCA dosing plan

PCA plan for Low Demand / High Infusion

Outcomes

Primary Outcome Measures

To determine whether there is a difference in time to first occurrence of a large improvement in daily average pain intensity between a High Demand/Low Infusion (HDLI) dosing vs. Low Demand/High Infusion (LDHI) dosing for parenteral opioid.

Secondary Outcome Measures

The reduction in opioid usage as assessed by total (or parenteral) opioid usage during hospitalization for vaso-occlusive pain, as well as opioid usage by day of hospitalization.
To compare the High Demand/Low Infusion (HDLI) vs. Low Demand/High Infusion (LDHI) treatment groups with respect to adverse events
Assessment of opioid withdrawal symptoms as reported post discharge in two follow-up telephone calls

Full Information

First Posted
October 20, 2009
Last Updated
April 16, 2013
Sponsor
Carelon Research
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT00999245
Brief Title
THE IMPROVE TRIAL: Improving Pain Management and Outcomes With Various Strategies of Patient-Controlled Analgesia (PCA)
Acronym
IMPROVE
Official Title
Improving Pain Management and Outcomes With Various Strategies of Patient-Controlled Analgesia (PCA)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Terminated
Why Stopped
Inability to meet target enrollment prior to ending of network in March 2011.
Study Start Date
January 2010 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Carelon Research
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Patient-Controlled Analgesia (PCA) means that the patient is in control of his/her pain medicine. In this study two (2) different treatment plans of Patient-Controlled Analgesia will be used to treat people with sickle cell disease who are admitted to the hospital for a pain crisis. The purpose of this study is to find out if one plan is better than the other in controlling sickle cell pain. If you are eligible for the study, you will be assigned by chance (like flipping a coin) to either get a higher continuous amount of the pain medicine with a smaller amount for pain as you need it, OR to get a smaller continuous amount of pain medicine with a larger amount of pain medicine as you need it. You or your study doctor can not choose which plan you receive, and you will not be told which one you have been assigned to. The doctors and nurses taking care of you will know which plan you are assigned to so they can safely and effectively take care of your pain. Some members of the study team will not know which plan you are on. We will give you morphine sulfate or hydromorphone (dilaudid) for your pain. These medicines are approved by the Food and Drug Administration (FDA) and have been used for a long time to relieve pain. If you have been treated for pain before with hydromorphone (dilaudid) and you prefer it to morphine, then you may choose to get it during the study. If you have not received hydromorphone (dilaudid) before or you do not have a preference then you will be given morphine for pain. The pain medicine will be given through the IV in your arm. You will receive morphine or hydromorphone continuously through the IV and will also be able to use the PCA machine to give yourself extra pain medicine as you need it for pain. You will need to push a button to give yourself extra medicine for pain. The amount of pain medicine you get on these plans is based on how much you weigh.
Detailed Description
The following things will be done for the study: Each day you are in the hospital someone from the study team who does not know your treatment assignment will come in 3 times during the day to ask you questions about your pain and how you are feeling. The doctors and nurses taking care of you will also do this as part of the routine care for your pain crisis. You will have your vital signs (blood pressure, heart rate, temperature) and oxygen level checked regularly as part of your routine care. The doctors and nurses may need to give you other medicines or do procedures that are not part of the study to take care of your pain crisis. They will talk with you about this. The doctors and nurses taking care of you while you are in the hospital will take care of you and treat your pain crisis just as they would do if you were not in this study. Being in this study will not interfere with the usual care and treatment you would receive. Each day you are in the hospital a member of the study team will have you answer questions about your pain, any side effects you are having, and how well you are able to move around. While you are in the hospital, you will wear an Actigraph Micro-Mini-Motion logger, a wristwatch type device that will keep track of how much you move around and how well you are sleeping. This will help us determine how well the treatment plan is relieving your pain level. You will wear the actigraph through Day 5 (Day 3 for children) of your hospital stay, or until you leave the hospital if you go home sooner. Each day you are in the hospital you will have blood drawn to check how well your kidneys and liver are working. These blood tests will be done at the same time as your regular blood tests whenever possible. We will collect about 2 teaspoons of blood from you for the study each day you are in the hospital. We will call you 3 days and 14 days after you leave the hospital. During these phone calls we will ask you questions about how you are feeling, the medications you are taking including those for pain, and any problems you have had since your discharge.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
High Demand / Low Infusion
Arm Type
Other
Arm Description
PCA dosing plan
Arm Title
Low Demand / High Infusion
Arm Type
Other
Arm Description
PCA plan for Low Demand / High Infusion
Intervention Type
Other
Intervention Name(s)
High Demand / Low Infusion
Other Intervention Name(s)
HDLI
Intervention Description
HDLI dosing plan will administer either morphine or hydromorphone using PCA. Dosing will be based on body weight.
Intervention Type
Other
Intervention Name(s)
PCA Dosing Plan
Other Intervention Name(s)
LDHI
Intervention Description
LDHI dosing plan will administer either morphine ot hydromorphone using PCA. Dosing will be based on body weight.
Primary Outcome Measure Information:
Title
To determine whether there is a difference in time to first occurrence of a large improvement in daily average pain intensity between a High Demand/Low Infusion (HDLI) dosing vs. Low Demand/High Infusion (LDHI) dosing for parenteral opioid.
Time Frame
Pain Intensity will be assessed 3 times a day between the hours of 7 AM and 7 PM on each day of the hospital stay
Secondary Outcome Measure Information:
Title
The reduction in opioid usage as assessed by total (or parenteral) opioid usage during hospitalization for vaso-occlusive pain, as well as opioid usage by day of hospitalization.
Time Frame
up to Inpatient Day 3 for pediatric subjects and Inpatient Day 5 for adults or discharge whichever occurs first.
Title
To compare the High Demand/Low Infusion (HDLI) vs. Low Demand/High Infusion (LDHI) treatment groups with respect to adverse events
Time Frame
Length of hospital stay
Title
Assessment of opioid withdrawal symptoms as reported post discharge in two follow-up telephone calls
Time Frame
Follow up phone calls on Day 3 and Day 14 after discharge from hospital

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Sickle Cell Disease: Hemoglobin diagnosis of SS (two copies of the hemoglobin S gene), SC (one copy of the hemoglobin S gene and one copy of the hemoglobin C gene), SD (one copy of the hemoglobin S gene and one copy of the hemoglobin D gene), or S-β thalassemia (β+ or β0) Male or female age ≥ 10 years. Typical vaso-occlusive pain that is not adequately controlled in an ambulatory or acute care setting and which is expected to require > 24 hours of hospital care. Pain Intensity Visual Analog (10 cm scale) score ≥ 4.5 cm, measured immediately after obtaining informed consent. Adults willing and able to give informed consent; parents willing and able to give permission for study participation by their children; minor subjects (ages 10-17) willing and able to provide assent. Ability to read/write English. Exclusion Criteria: Medical Indication Presence of significant liver disease (ALT > 3 times institutional upper limit of normal, or direct bilirubin > 0.8 mg/dl within preceding 3 months) Presence of significant renal dysfunction (within preceding 3 months, creatinine ≥ 1.2 mg/dl for ages >18 yrs, or ages 10-18 yrs creatinine ≥ 1.0 mg/dl) Oxygen saturation by pulse oximetry ≤ 92% on room air at study entry Any other medical condition that renders the subject unable to or unlikely to complete the study or which would interfere with optimal participation in the study or which poses significant risk to the subject from study treatment including but not limited to: Concurrent acute chest syndrome Right upper quadrant pain Symptomatic sleep apnea Brain injury or doses of opioids that preclude potential subjects' capacity to give informed consent. Known (documented) hypersensitivity/intolerance to morphine and/or hydromorphone. Clinically significant opioid tolerance in the opinion of the investigator that precludes safe and/or effective dosing or requires, under current management, receiving the following long-acting oral opioids: Methadone 40 mg/day Sustained/Extended release oral morphine 120 mg /day Oxycodone 80 mg/day Known pregnancy or currently breastfeeding. Poor venous access that in the investigator's judgment would preclude maintaining an IV throughout the admission. Currently participating in another research study. Previously randomized in the IMPROVE trial. Pain management in emergency department or Day Hospital ≥ 12 hours prior to decision to admit for inpatient care. Subject or physician preference for treatment with opioids other than morphine or hydromorphone.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlton Dampier, MD
Organizational Affiliation
Sickle Cell Disease Clinical Research Network
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Wally Smith, MD
Organizational Affiliation
Sickle Cell Disease Clinical Research Network
Official's Role
Study Chair
Facility Information:
Facility Name
Children's Hospital and Research Center
City
Oakland
State/Province
California
Country
United States
Facility Name
Yale-New Haven Medical Center,
City
New Haven
State/Province
Connecticut
Country
United States
Facility Name
A.I. duPont Hospital for Children
City
Wilmington
State/Province
Delaware
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
Country
United States
Facility Name
Howard University Hospital
City
Washington
State/Province
District of Columbia
Country
United States
Facility Name
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Medical College of Georgia
City
Augusta
State/Province
Georgia
Country
United States
Facility Name
Children's Memorial Hospital
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
University of Illinois Sickle Cell Center
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Kosair Children's Hospital
City
Louisville
State/Province
Kentucky
Country
United States
Facility Name
Children's Hospital at Sinai
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
Johns Hopkins
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
Country
United States
Facility Name
Boston Medical Center
City
Boston,
State/Province
Massachusetts
Country
United States
Facility Name
Children's Hospital Boston
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
Country
United States
Facility Name
Interfaith Medical Center
City
Brooklyn
State/Province
New York
Country
United States
Facility Name
New York Methodist Hospital
City
Brooklyn
State/Province
New York
Country
United States
Facility Name
The University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
St. Christopher's Hospital for Children
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
Country
United States
Facility Name
Virginia Commonwealth University Health Systems
City
Richmond
State/Province
Virginia
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23539110
Citation
Dampier CD, Smith WR, Wager CG, Kim HY, Bell MC, Miller ST, Weiner DL, Minniti CP, Krishnamurti L, Ataga KI, Eckman JR, Hsu LL, McClish D, McKinlay SM, Molokie R, Osunkwo I, Smith-Whitley K, Telen MJ; Sickle Cell Disease Clinical Research Network (SCDCRN). IMPROVE trial: a randomized controlled trial of patient-controlled analgesia for sickle cell painful episodes: rationale, design challenges, initial experience, and recommendations for future studies. Clin Trials. 2013 Apr;10(2):319-31. doi: 10.1177/1740774513475850.
Results Reference
derived

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THE IMPROVE TRIAL: Improving Pain Management and Outcomes With Various Strategies of Patient-Controlled Analgesia (PCA)

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