Sickle Cell DiseasePhase 2/3MAGiCNCT01197417
Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis
A Phase 2/3 study testing Intravenous Magnesium Sulfate in people with Sickle Cell Disease, run by Medical College of Wisconsin at 8 sites in United States.
Trial summary
The purpose of this study is to determine the safety and efficacy of intravenous magnesium in shortening the duration of a pain crisis and to determine the health-related quality of life and short term outcomes of children treated with intravenous magnesium during an acute pain crisis. Read more about this study
- Who is it for?
- Ages 4 to 21 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Intravenous Magnesium Sulfate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 208 participants
- Where
- 8 sitesUnited States
- Study dates
- Dec 2010to Mar 2014
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 4 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- age 4-21 years, inclusive
- Sickle cell anemia (Hb SS) or Sickle beta zero thalassemia disease (Hb Sβ°)
- failed intravenous opioid pain management in the emergency department prior to the decision to admit the patient
- admitted to the inpatient unit for sickle cell pain crisis
Who cannot join
- patient received more than 12 hours of intravenous pain medication prior to enrollment
- previous enrollment in this study (only one admission per child is eligible)
- history of allergy/intolerance to both intravenous morphine and hydromorphone
- known other cause for pain (avascular necrosis, gall bladder disease, priapism, etc.)
- patient with greater than 10 admissions for pain crisis in the past year
- patient maintained on daily opioids or chronic transfusions for chronic sickle cell pain
Show all 16Show fewer
- transfusion within the previous two months
- known kidney or liver failure (elevation of liver function tests does not warrant exclusion)
- known pulmonary hypertension
- pregnancy
- diagnosis of bacterial infection, fever ≥39.5°C, acute chest syndrome, hemodynamic instability or sepsis
- current oral magnesium supplementation or current enrollment in another therapeutic study protocol
- previously diagnosed clinical stroke
- current or planned use of neuromuscular blocker, nifedipine, ritodrine, or terbutaline
- allergy to magnesium sulfate
- discharge from an inpatient unit within 72 hours of arrival in the emergency department for the current pain crisis
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Nationwide Children's Hospital
Columbus, Ohio, 43205
Children's Hospital of Michigan
Detroit, Michigan, 48201
Baylor College of Medicine
Houston, Texas, 77030
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospital of Philadelphia Research Institute
Philadelphia, Pennsylvania, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
The purpose of this study is to determine the safety and efficacy of intravenous magnesium in shortening the duration of a pain crisis and to determine the health-related quality of life and short term outcomes of children treated with intravenous magnesium during an acute pain crisis.
Read the detailed description
It is well known that children with sickle cell disease are at risk for acute pain crises. The usual treatment for these pain crises, intravenous fluids and pain medicines such as morphine, has changed little over the past three decades. In a pilot study, the addition of intravenous magnesium to standard therapy decreased length of stay; however, this study was not randomized, not blinded, not placebo-controlled, and not adequately powered to assess safety.
We will conduct a multi-center, randomized, double-blind, placebo controlled trial of about 208 children, ages 4-21 years. Patients will be randomized to receive intravenous magnesium sulfate or placebo every 8 hours for a total of 6 doses, or until discharge. Patients will return for a routine clinic visit up to 3 months after discharge for a baseline assessment. Patients will also complete health-related quality of life measures at 4 timepoints throughout the study.
- Conditions
- Sickle Cell Disease
- Being tested
- Intravenous Magnesium Sulfate, Normal Saline Placebo
- Keywords
- Sickle Cell Disease, Magnesium Sulfate, Pediatric
- 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.
Intravenous Magnesium SulfateDrug
40 mg/kg (max 2.4 grams), infused at a concentration of 40 mg/ml (1 ml/kg, max 60 ml), every 8 hours for a total of 6 doses
Normal Saline PlaceboDrug
(1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses
| Study group | Role | What they receive |
|---|---|---|
| Magnesium group | Experimental | Intravenous Magnesium Sulfate Receives: Drug: Intravenous Magnesium Sulfate |
| Placebo group | Placebo comparator | Normal Saline placebo Receives: Drug: Normal Saline Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hospital Length of Stay (Hours)
Measured: From the time of the start of first study med infusion until hospital discharge or 12 hours after the last IV opioid, whichever occurs first, up to 10 days post enrollment
Secondary outcomes (6)
Number of Morphine Equivalents Per Kilogram of Body Weight Used During Hospitalization
Measured: Total morphine equivalents used during the hospitalization will be recorded on the day of discharge, up to 10 days post enrollment
Hypotension Associated With Infusion
For each study drug infusion, systolic blood pressure (SBP) was measured just prior to the start of the infusion and again every 10 minutes until 30 minutes until the end of the infusion. Hypotension was defined as a greater than 20% reduction in SBP relative to corresponding baseline measurement for any study drug infusion.
Measured: Blood pressure will be monitored every 8 hours, concurrent with each infusion, and for 20-30 minutes after infusion completion, until discharge, up to 2 days post enrollment
Warm Sensation Associated With Study Drug Infusion
Patient spontaneously reported feelings of warmth during any study drug infusion.
Measured: Patient-reported warm sensation upon infusion will be monitored every 8 hours, concurrent with each infusion, and for 20-30 minutes after infusion completion, until discharge, up to 2 days post enrollment
Rehospitalization
Measured: Rehospitalization will be measured at 7 days post discharge and at the follow-up visit (on average, 30 days post discharge)
Development of Acute Chest Syndrome (ACS)
Measured: Patients will be monitored daily, on average, during their length of stay until discharge, up to 10 days post enrollment
Hospital Length of Stay
Measured: Start of first study drug infusion to actual hospital discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2010 (estimated)
- Study startDec 2010
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 208 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Collaborators
- Pediatric Emergency Care Applied Research Network
- Responsible party
- Sponsor
- Investigators
- David Brousseau, MD, MS, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01197417
- Sponsor's protocol ID
- PECARN 025
- Acronym
- MAGiC
- Status last verified
- Dec 2015
- First submitted
- 31 Aug 2010
- Last updated
- 27 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Brousseau DC, Scott JP, Badaki-Makun O, Darbari DS, Chumpitazi CE, Airewele GE, Ellison AM, Smith-Whitley K, Mahajan P, Sarnaik SA, Casper TC, Cook LJ, Dean JM, Leonard J, Hulbert ML, Powell EC, Liem RI, Hickey R, Krishnamurti L, Hillery CA, Nimmer M, Panepinto JA; Pediatric Emergency Care Applied Research Network (PECARN). A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children. Blood. 2015 Oct 1;126(14):1651-7. doi: 10.1182/blood-2015-05-647107. Epub 2015 Jul 31.
PubMed 26232172Panepinto JA, Paul Scott J, Badaki-Makun O, Darbari DS, Chumpitazi CE, Airewele GE, Ellison AM, Smith-Whitley K, Mahajan P, Sarnaik SA, Charles Casper T, Cook LJ, Leonard J, Hulbert ML, Powell EC, Liem RI, Hickey R, Krishnamurti L, Hillery CA, Brousseau DC; Pediatric Emergency Care Applied Research Network (PECARN). Determining the longitudinal validity and meaningful differences in HRQL of the PedsQL Sickle Cell Disease Module. Health Qual Life Outcomes. 2017 Jun 12;15(1):124. doi: 10.1186/s12955-017-0700-2.
PubMed 28606098Badaki-Makun O, Scott JP, Panepinto JA, Casper TC, Hillery CA, Dean JM, Brousseau DC; Pediatric Emergency Care Applied Research Network (PECARN) Magnesium in Sickle Cell Crisis (MAGiC) Study Group. Intravenous magnesium for pediatric sickle cell vaso-occlusive crisis: methodological issues of a randomized controlled trial. Pediatr Blood Cancer. 2014 Jun;61(6):1049-54. doi: 10.1002/pbc.24925. Epub 2014 Jan 17.
PubMed 24443249
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis
- ClinicalTrials.gov ID
- NCT01197417
- Acronym / sponsor ID
- MAGiC / PECARN 025
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle Cell Disease, Magnesium Sulfate, Pediatric
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 208 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Collaborators
- Pediatric Emergency Care Applied Research Network
- Study start
- Dec 2010
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 9 Sep 2010 (estimated)
- Results
- Posted 7 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the safety and efficacy of intravenous magnesium in shortening the duration of a pain crisis and to determine the health-related quality of life and short term outcomes of children treated with intravenous magnesium during an acute pain crisis.
Detailed description
It is well known that children with sickle cell disease are at risk for acute pain crises. The usual treatment for these pain crises, intravenous fluids and pain medicines such as morphine, has changed little over the past three decades. In a pilot study, the addition of intravenous magnesium to standard therapy decreased length of stay; however, this study was not randomized, not blinded, not placebo-controlled, and not adequately powered to assess safety.
We will conduct a multi-center, randomized, double-blind, placebo controlled trial of about 208 children, ages 4-21 years. Patients will be randomized to receive intravenous magnesium sulfate or placebo every 8 hours for a total of 6 doses, or until discharge. Patients will return for a routine clinic visit up to 3 months after discharge for a baseline assessment. Patients will also complete health-related quality of life measures at 4 timepoints throughout the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Magnesium group | Experimental | Drug: Intravenous Magnesium SulfateIntravenous Magnesium Sulfate |
| Placebo group | Placebo comparator | Drug: Normal Saline PlaceboNormal Saline placebo |
Who may qualify
- Ages
- 4 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- age 4-21 years, inclusive
- Sickle cell anemia (Hb SS) or Sickle beta zero thalassemia disease (Hb Sβ°)
- failed intravenous opioid pain management in the emergency department prior to the decision to admit the patient
- admitted to the inpatient unit for sickle cell pain crisis
Key exclusion criteria (16 listed)
- patient received more than 12 hours of intravenous pain medication prior to enrollment
- previous enrollment in this study (only one admission per child is eligible)
- history of allergy/intolerance to both intravenous morphine and hydromorphone
- known other cause for pain (avascular necrosis, gall bladder disease, priapism, etc.)
- patient with greater than 10 admissions for pain crisis in the past year
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 |
|---|---|---|
| Intravenous Magnesium Sulfate40 mg/kg (max 2.4 grams), infused at a concentration of 40 mg/ml (1 ml/kg, max 60 ml), every 8 hours for a total of 6 doses | Drug | Magnesium group |
| Normal Saline Placebo(1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses | Drug | Placebo group |
Primary outcome
Hospital Length of Stay (Hours)
Time frame: From the time of the start of first study med infusion until hospital discharge or 12 hours after the last IV opioid, whichever occurs first, up to 10 days post enrollment
6 secondary outcomes
Number of Morphine Equivalents Per Kilogram of Body Weight Used During Hospitalization
Time frame: Total morphine equivalents used during the hospitalization will be recorded on the day of discharge, up to 10 days post enrollment
Hypotension Associated With Infusion
Time frame: Blood pressure will be monitored every 8 hours, concurrent with each infusion, and for 20-30 minutes after infusion completion, until discharge, up to 2 days post enrollment
Warm Sensation Associated With Study Drug Infusion
Time frame: Patient-reported warm sensation upon infusion will be monitored every 8 hours, concurrent with each infusion, and for 20-30 minutes after infusion completion, until discharge, up to 2 days post enrollment
Rehospitalization
Time frame: Rehospitalization will be measured at 7 days post discharge and at the follow-up visit (on average, 30 days post discharge)
Development of Acute Chest Syndrome (ACS)
Time frame: Patients will be monitored daily, on average, during their length of stay until discharge, up to 10 days post enrollment
Hospital Length of Stay
Time frame: Start of first study drug infusion to actual hospital discharge
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26232172Brousseau DC, Scott JP, Badaki-Makun O, Darbari DS, Chumpitazi CE, Airewele GE, Ellison AM, Smith-Whitley K, Mahajan P, Sarnaik SA, Casper TC, Cook LJ, Dean JM, Leonard J, Hulbert ML, Powell EC, Liem RI, Hickey R, Krishnamurti L, Hillery CA, Nimmer M, Panepinto JA; Pediatric Emergency Care Applied Research Network (PECARN). A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children. Blood. 2015 Oct 1;126(14):1651-7. doi: 10.1182/blood-2015-05-647107. Epub 2015 Jul 31.
- Derived from this study: PubMed 28606098Panepinto JA, Paul Scott J, Badaki-Makun O, Darbari DS, Chumpitazi CE, Airewele GE, Ellison AM, Smith-Whitley K, Mahajan P, Sarnaik SA, Charles Casper T, Cook LJ, Leonard J, Hulbert ML, Powell EC, Liem RI, Hickey R, Krishnamurti L, Hillery CA, Brousseau DC; Pediatric Emergency Care Applied Research Network (PECARN). Determining the longitudinal validity and meaningful differences in HRQL of the PedsQL Sickle Cell Disease Module. Health Qual Life Outcomes. 2017 Jun 12;15(1):124. doi: 10.1186/s12955-017-0700-2.
- Derived from this study: PubMed 24443249Badaki-Makun O, Scott JP, Panepinto JA, Casper TC, Hillery CA, Dean JM, Brousseau DC; Pediatric Emergency Care Applied Research Network (PECARN) Magnesium in Sickle Cell Crisis (MAGiC) Study Group. Intravenous magnesium for pediatric sickle cell vaso-occlusive crisis: methodological issues of a randomized controlled trial. Pediatr Blood Cancer. 2014 Jun;61(6):1049-54. doi: 10.1002/pbc.24925. Epub 2014 Jan 17.
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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.
David Brousseau, MD, MS principal investigator
Medical College of Wisconsin
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Intravenous Magnesium Sulfate in people with Sickle Cell Disease, run by Medical College of Wisconsin at 8 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 4 inclusion and 16 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: finished, as of the sponsor's last update on 27 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Yes. Results are posted in the registry (first posted 7 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Hospital Length of Stay (Hours) (time frame: From the time of the start of first study med infusion until hospital discharge or 12 hours after the last IV opioid, whichever occurs first, up to 10 days post enrollment). 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 NCT01197417, which also lists 3 linked publications.
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 27 Jan 2016.