THE IMPROVE TRIAL: Improving Pain Management and Outcomes With Various Strategies of Patient-Controlled Analgesia (PCA)
Information source: New England Research Institutes
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Sickle Cell Disease
Intervention: High Demand / Low Infusion (Other); PCA Dosing Plan (Other)
Phase: Phase 3
Sponsored by: New England Research Institutes
Official(s) and/or principal investigator(s):
Carlton Dampier, MD, Study Chair, Affiliation: Sickle Cell Disease Clinical Research Network
Wally Smith, MD, Study Chair, Affiliation: Sickle Cell Disease Clinical Research Network
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.
Official title: Improving Pain Management and Outcomes With Various Strategies of Patient-Controlled Analgesia (PCA)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: 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.
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
The following things will be done for the study:
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
Minimum age: 10 Years.
Maximum age: N/A.
- 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.
- 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
Locations and Contacts
Children's Hospital and Research Center, Oakland, California, United States
Yale-New Haven Medical Center,, New Haven, Connecticut, United States
A.I. duPont Hospital for Children, Wilmington, Delaware, United States
Children's National Medical Center, Washington, District of Columbia, United States
Howard University Hospital, Washington, District of Columbia, United States
Emory University School of Medicine, Atlanta, Georgia, United States
Medical College of Georgia, Augusta, Georgia, United States
Children's Memorial Hospital, Chicago, Illinois, United States
University of Illinois Sickle Cell Center, Chicago, Illinois, United States
Kosair Children's Hospital, Louisville, Kentucky, United States
Children's Hospital at Sinai, Baltimore, Maryland, United States
Johns Hopkins, Baltimore, Maryland, United States
National Institutes of Health Clinical Center, Bethesda, Maryland, United States
Boston Medical Center, Boston,, Massachusetts, United States
Children's Hospital Boston, Boston, Massachusetts, United States
University of Mississippi Medical Center, Jackson, Mississippi, United States
Interfaith Medical Center, Brooklyn, New York, United States
New York Methodist Hospital, Brooklyn, New York, United States
The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Duke University Medical Center, Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Nationwide Children's Hospital, Columbus, Ohio, United States
Ohio State University, Columbus, Ohio, United States
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
St. Christopher's Hospital for Children, Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States
Texas Children's Hospital, Houston, Texas, United States
Virginia Commonwealth University Health Systems, Richmond, Virginia, United States
Starting date: January 2010
Last updated: April 16, 2013