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

Condition(s) targeted: Sickle Cell Disease

Intervention: High Demand / Low Infusion (Other); PCA Dosing Plan (Other)

Phase: Phase 3

Status: Recruiting

Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)

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, Control: Dose Comparison, 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 HDLI dosing schedule vs. LDHI dosing schedule for parenteral opioid.

Secondary outcome:

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 HDLI and LDHI treatment groups with respect to adverse events

Assessment of opioid withdrawal symptoms as reported post discharge in two follow-up telephone calls

Detailed description: 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 MicroMini-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. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Sickle Cell Disease: Hb SS, SC, SD, S beta Thal, S beta Thal+.

- 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 ED 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.

Children's Hospital and Research Center, Oakland, California, United States; Recruiting
Mark Walters, MD, Email: mwalters@mail.cho.org
Mark Walters, MD, Principal Investigator

Yale-New Haven Medical Center,, New Haven, Connecticut, United States; Recruiting
Farzana Pashankar, MD, Email: farzana.pashankar@yale.edu
Farzana Pashankar, MD, Principal Investigator

A.I. duPont Hospital for Children, Wilmington, Delaware, United States; Recruiting
Robin Miller, MD, Email: rmiller@nemours.org
Robin Miller, MD, Principal Investigator

Children's National Medical Center, Washington, District of Columbia, United States; Recruiting
Lewis Hsu, MD, Email: LHsu@cnmc.org
Lewis Hsu, MD, Principal Investigator

Howard University Hospital, Washington, District of Columbia, United States; Recruiting
Victor R. Gordeuk, MD, Email: vgordeuk@howard.edu
Victor R. Gordeuk, MD, Principal Investigator

Emory University School of Medicine, Atlanta, Georgia, United States; Recruiting
Peter Lane, MD, Email: plane@emory.edu
Peter Lane, MD, Principal Investigator

Medical College of Georgia, Augusta, Georgia, United States; Recruiting
Abdullah Kutlar, MD, Email: akutlar@mcg.edu
Abdullah Kutlar, MD, Principal Investigator

Children's Memorial Hospital, Chicago, Illinois, United States; Recruiting
A. Kyle Mack, MD, Email: akmack@childrensmemorial.org
A. Kyle Mack, MD, Principal Investigator

University of Illinois Sickle Cell Center, Chicago, Illinois, United States; Recruiting
Richard Labotka, MD, Email: richardl@uic.edu
Richard Labotka, MD, Principal Investigator

Kosair Children's Hospital, Louisville, Kentucky, United States; Recruiting
Salvatore Bertolone, MD, Email: sjbert01@louisville.edu
Salvatore Bertolone, MD, Principal Investigator

Children's Hospital at Sinai, Baltimore, Maryland, United States; Recruiting
Jason Fixler, MD, Email: Jfixler@lifebridgehealth.org
Jason Fixler, MD, Principal Investigator

Johns Hopkins, Baltimore, Maryland, United States; Recruiting
Jeffrey Keefer, MD, PhD, Email: jrkeefer@jhmi.edu
Jeffrey Keefer, MD, PhD, Principal Investigator

National Institutes of Health Clinical Center, Bethesda, Maryland, United States; Recruiting
Caterina Minniti, MD, Email: minnitic@nhlbi.nih.gov
Caterina Minniti, MD, Principal Investigator

Children's Hospital Boston, Boston, Massachusetts, United States; Recruiting
Matthew Heeney, MD, Email: matthew.heeney@childrens.harvard.edu
Matthew Heeney, MD, Principal Investigator

Boston Medical Center, Boston,, Massachusetts, United States; Recruiting
Lillian McMahon, MD, Email: lmcmahon@bu.edu
Lillian McMahon, MD, Principal Investigator

University of Mississippi Medical Center, Jackson, Mississippi, United States; Recruiting
Rathi V. Iyer, MD, Email: riyer@ped.umsmed.edu
Rathi V. Iyer, MD, Principal Investigator

Interfaith Medical Center, Brooklyn, New York, United States; Recruiting
Edouard Guillaume, MD, Email: eguillaume611@aol.com
Edouard Guillaume, MD, Principal Investigator

New York Methodist Hospital, Brooklyn, New York, United States; Recruiting
Rita Bellevue, MD, Email: rib9001@nyp.org
Rita Bellevue, MD, Principal Investigator

The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States; Recruiting
Kenneth I. Ataga, MD, Email: kataga@med.unc.edu
Kenneth I. Ataga, MD, Principal Investigator

Duke University Medical Center, Durham, North Carolina, United States; Recruiting
Laura DeCastro, MD, Email: decas004@mc.duke.edu
Laura DeCastro, MD, Principal Investigator

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States; Recruiting
Clint Joiner, MD, PhD, Email: Clinton.joiner@chmcc.org
Clint Joiner, MD, PhD, Principal Investigator

Nationwide Children's Hospital, Columbus, Ohio, United States; Recruiting
Melissa Rhodes, MD, Email: Melissa.Rhodes@nationwidechildrens.org
Melissa Rhodes, MD, Principal Investigator

Ohio State University, Columbus, Ohio, United States; Recruiting
Eric Kraut, MD, Email: Eric.Kraut@osumc.edu
Eric Kraut, MD, Principal Investigator

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States; Recruiting
Kim Smith-Whitley, MD, Email: whitleyk@email.chop.edu
Kim Smith-Whitley, MD, Principal Investigator

St. Christopher's Hospital for Children, Philadelphia, Pennsylvania, United States; Recruiting
Norma Lerner, MD, Email: norma.lerner@tenethealth.com
Norma Lerner, MD, Principal Investigator

Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States; Recruiting
Lakshmanan Krishnamurti, MD, Email: krislx@chp.edu
Lakshmanan Krishnamurti, MD, Principal Investigator

Texas Children's Hospital, Houston, Texas, United States; Recruiting
Brigitta Mueller, MD, Email: bumuelle@txccc.org
Brigitta Mueller, MD, Principal Investigator

Virginia Commonwealth University Health Systems, Richmond, Virginia, United States; Recruiting
Wally Smith, MD, Email: wrsmith@vcu.edu
Wally Smith, MD, Principal Investigator

Starting date: January 2010
Last updated: February 22, 2010