Sickle Cell DiseasePhase 3IMPROVENCT00999245
THE IMPROVE TRIAL: Improving Pain Management and Outcomes With Various Strategies of Patient-Controlled Analgesia (PCA)
A Phase 3 study testing High Demand / Low Infusion and PCA Dosing Plan in people with Sickle Cell Disease, run by Carelon Research at 28 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- High Demand / Low Infusion and PCA Dosing Plan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 28 sitesUnited States
- Study dates
- Jan 2010to Jun 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 20Show fewer
- 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.
Trial locations and contacts
28 sites in 1 country.
28 sites in 1 country
United States28 sites
Emory University School of Medicine
Atlanta, Georgia
Medical College of Georgia
Augusta, Georgia
Children's Hospital at Sinai
Baltimore, Maryland
Johns Hopkins
Baltimore, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland
Boston Medical Center
Boston, Massachusetts
Children's Hospital Boston
Boston, Massachusetts
Interfaith Medical Center
Brooklyn, New York
New York Methodist Hospital
Brooklyn, New York
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina
Children's Memorial Hospital
Chicago, Illinois
University of Illinois Sickle Cell Center
Chicago, Illinois
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio
Nationwide Children's Hospital
Columbus, Ohio
Ohio State University
Columbus, Ohio
Duke University Medical Center
Durham, North Carolina
Texas Children's Hospital
Houston, Texas
University of Mississippi Medical Center
Jackson, Mississippi
Kosair Children's Hospital
Louisville, Kentucky
Yale-New Haven Medical Center,
New Haven, Connecticut
Children's Hospital and Research Center
Oakland, California
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania
Virginia Commonwealth University Health Systems
Richmond, Virginia
Children's National Medical Center
Washington D.C., District of Columbia
Howard University Hospital
Washington D.C., District of Columbia
A.I. duPont Hospital for Children
Wilmington, Delaware
About this study
Official title: Improving Pain Management and Outcomes With Various Strategies of Patient-Controlled Analgesia (PCA)
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.
Read more
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.
Read the 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.
- Conditions
- Sickle Cell Disease
- Being tested
- High Demand / Low Infusion, PCA Dosing Plan
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High Demand / Low InfusionOther
Also called HDLI
HDLI dosing plan will administer either morphine or hydromorphone using PCA. Dosing will be based on body weight.
PCA Dosing PlanOther
Also called LDHI
LDHI dosing plan will administer either morphine ot hydromorphone using PCA. Dosing will be based on body weight.
| Study group | Role | What they receive |
|---|---|---|
| High Demand / Low Infusion | Other | PCA dosing plan Receives: Other: High Demand / Low Infusion |
| Low Demand / High Infusion | Other | PCA plan for Low Demand / High Infusion Receives: Other: PCA Dosing Plan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: Length of hospital stay
Assessment of opioid withdrawal symptoms as reported post discharge in two follow-up telephone calls
Measured: Follow up phone calls on Day 3 and Day 14 after discharge from hospital
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2009 (estimated)
- Study startJan 2010
- Primary completionJun 2010
- Study completionJun 2010
Why it stopped: Inability to meet target enrollment prior to ending of network in March 2011.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carelon Research
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Carlton Dampier, MD, Study chair, Sickle Cell Disease Clinical Research NetworkWally Smith, MD, Study chair, Sickle Cell Disease Clinical Research Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00999245
- Sponsor's protocol ID
- 683
- Other IDs
- U10HL083721
- Acronym
- IMPROVE
- Status last verified
- Apr 2013
- First submitted
- 20 Oct 2009
- Last updated
- 18 Apr 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 23539110
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Pain Management and Outcomes With Various Strategies of Patient-Controlled Analgesia (PCA)
- ClinicalTrials.gov ID
- NCT00999245
- Acronym / sponsor ID
- IMPROVE / 683
- Conditions
- Sickle Cell Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inability to meet target enrollment prior to ending of network in March 2011.
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Carelon ResearchUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jan 2010
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 21 Oct 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High Demand / Low Infusion | Other | Other: High Demand / Low InfusionPCA dosing plan |
| Low Demand / High Infusion | Other | Other: PCA Dosing PlanPCA plan for Low Demand / High Infusion |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (20 listed)
- Medical Indication
- 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:
- Known pregnancy or currently breastfeeding.
- Poor venous access that in the investigator's judgment would preclude maintaining an IV throughout the admission.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High Demand / Low InfusionAlso: HDLIHDLI dosing plan will administer either morphine or hydromorphone using PCA. Dosing will be based on body weight. | Other | High Demand / Low Infusion |
| PCA Dosing PlanAlso: LDHILDHI dosing plan will administer either morphine ot hydromorphone using PCA. Dosing will be based on body weight. | Other | Low Demand / High Infusion |
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.
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
3 secondary outcomes
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.
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
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
Results and safety
The study was stopped early (reason given: Inability to meet target enrollment prior to ending of network in March 2011.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2013.
- Derived from this study: PubMed 23539110Dampier 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carlton Dampier, MD study chair
Sickle Cell Disease Clinical Research Network
Wally Smith, MD study chair
Sickle Cell Disease Clinical Research Network
28 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing High Demand / Low Infusion and PCA Dosing Plan in people with Sickle Cell Disease, run by Carelon Research at 28 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Inability to meet target enrollment prior to ending of network in March 2011.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00999245, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2013.