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

NCT00999245 | Terminated Phase 3 DMC

• 2 other identifiers: 683U10HL083721
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 28

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.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (3)

• 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.

  up to Inpatient Day 3 for pediatric subjects and Inpatient Day 5 for adults or discharge whichever occurs first.

• To compare the High Demand/Low Infusion (HDLI) vs. Low Demand/High Infusion (LDHI) treatment groups with respect to adverse events

  Length of hospital stay

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

  Follow up phone calls on Day 3 and Day 14 after discharge from hospital

Study Arms (2)

High Demand / Low Infusion

OTHER

PCA dosing plan

Other: High Demand / Low Infusion

Low Demand / High Infusion

OTHER

PCA plan for Low Demand / High Infusion

Other: PCA Dosing Plan

Interventions

High Demand / Low Infusion OTHER

HDLI dosing plan will administer either morphine or hydromorphone using PCA. Dosing will be based on body weight.

Also known as: HDLI

High Demand / Low Infusion

PCA Dosing Plan OTHER

LDHI dosing plan will administer either morphine ot hydromorphone using PCA. Dosing will be based on body weight.

Also known as: LDHI

Low Demand / High Infusion

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Carelon Research: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (28)

Children's Hospital and Research Center

Oakland, California, United States

Location

Yale-New Haven Medical Center,

New Haven, Connecticut, United States

Location

A.I. duPont Hospital for Children

Wilmington, Delaware, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, United States

Location

Howard University Hospital

Washington D.C., District of Columbia, United States

Location

Emory University School of Medicine

Atlanta, Georgia, United States

Location

Medical College of Georgia

Augusta, Georgia, United States

Location

Children's Memorial Hospital

Chicago, Illinois, United States

Location

University of Illinois Sickle Cell Center

Chicago, Illinois, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, United States

Location

Children's Hospital at Sinai

Baltimore, Maryland, United States

Location

Johns Hopkins

Baltimore, Maryland, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Location

Boston Medical Center

Boston, Massachusetts, United States

Location

Children's Hospital Boston

Boston, Massachusetts, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, United States

Location

Interfaith Medical Center

Brooklyn, New York, United States

Location

New York Methodist Hospital

Brooklyn, New York, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Location

Duke University Medical Center

Durham, North Carolina, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, United States

Location

Ohio State University

Columbus, Ohio, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Location

Texas Children's Hospital

Houston, Texas, United States

Location

Virginia Commonwealth University Health Systems

Richmond, Virginia, United States

Location

Related Publications (1)

• 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.

  PMID: 23539110 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Carlton Dampier, MD

  Sickle Cell Disease Clinical Research Network

  STUDY CHAIR

• Wally Smith, MD

  Sickle Cell Disease Clinical Research Network

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2009
• First Posted: October 21, 2009
• Study Start: January 1, 2010
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: April 18, 2013

Record last verified: 2013-04

Locations

US (28)