Trial Outcomes & Findings for Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis (NCT NCT01197417)

NCT ID: NCT01197417

Last Updated: 2016-01-27

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 208 participants
• Primary outcome timeframe: 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
• Results posted on: 2016-01-27

Participant Flow

Participant milestones

Measure	Magnesium Group Intravenous Magnesium Sulfate Intravenous Magnesium Sulfate: 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	Placebo Group Normal Saline placebo Normal Saline Placebo: (1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses
Overall Study STARTED	104	104
Overall Study Received Study Drug	101	103
Overall Study COMPLETED	96	86
Overall Study NOT COMPLETED	8	18

Reasons for withdrawal

Measure	Magnesium Group Intravenous Magnesium Sulfate Intravenous Magnesium Sulfate: 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	Placebo Group Normal Saline placebo Normal Saline Placebo: (1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses
Overall Study Physician Decision	3	2
Overall Study Withdrawal by Subject	2	4
Overall Study Site miscommunication	0	1
Overall Study Subject transferred to intensive care	0	1
Overall Study Not consented in time to receive drug	0	1
Overall Study Hypotension	1	2
Overall Study Found to be ineligible	2	5
Overall Study No 25-hour magnesium level	0	2

Baseline Characteristics

Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis

Baseline characteristics by cohort

Measure	Magnesium Group n=104 Participants Intravenous Magnesium Sulfate Intravenous Magnesium Sulfate: 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	Placebo Group n=104 Participants Normal Saline placebo Normal Saline Placebo: (1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses	Total n=208 Participants Total of all reporting groups
Age, Categorical <=18 years	93 Participants n=5 Participants	88 Participants n=7 Participants	181 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	16 Participants n=7 Participants	27 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	13.4 years STANDARD_DEVIATION 4.5 • n=5 Participants	13.8 years STANDARD_DEVIATION 4.8 • n=7 Participants	13.6 years STANDARD_DEVIATION 4.7 • n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	57 Participants n=7 Participants	108 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	47 Participants n=7 Participants	100 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	96 Participants n=5 Participants	94 Participants n=7 Participants	190 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	99 participants n=5 Participants	94 participants n=7 Participants	193 participants n=5 Participants
Race/Ethnicity, Customized White	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized More than one race	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized Unknown or not reported	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United States	104 participants n=5 Participants	104 participants n=7 Participants	208 participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Population: All participants who received at least one dose of study drug and who did not withdraw from data collection prior to outcome

Outcome measures

Measure	Magnesium Group n=100 Participants Intravenous Magnesium Sulfate Intravenous Magnesium Sulfate: 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	Placebo Group n=102 Participants Normal Saline placebo Normal Saline Placebo: (1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses
Hospital Length of Stay (Hours)	56 hours Interval 27.0 to 109.0	47 hours Interval 24.0 to 99.0

SECONDARY outcome

Timeframe: Total morphine equivalents used during the hospitalization will be recorded on the day of discharge, up to 10 days post enrollment

Population: All participants who received at least one dose of study drug and who did not withdraw from data collection prior to either hospital discharge or 12 hours after last intravenous opioid.

Outcome measures

Measure	Magnesium Group n=100 Participants Intravenous Magnesium Sulfate Intravenous Magnesium Sulfate: 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	Placebo Group n=102 Participants Normal Saline placebo Normal Saline Placebo: (1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses
Number of Morphine Equivalents Per Kilogram of Body Weight Used During Hospitalization	1.46 mg Morphine/kg Interval 0.55 to 3.32	1.28 mg Morphine/kg Interval 0.4 to 3.29

SECONDARY outcome

Timeframe: 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

Population: All participants who received at least one dose of study drug

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.

Outcome measures

Measure	Magnesium Group n=101 Participants Intravenous Magnesium Sulfate Intravenous Magnesium Sulfate: 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	Placebo Group n=103 Participants Normal Saline placebo Normal Saline Placebo: (1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses
Hypotension Associated With Infusion	4 Participant	1 Participant

SECONDARY outcome

Timeframe: 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

Population: All participants who received at least one dose of study drug.

Patient spontaneously reported feelings of warmth during any study drug infusion.

Outcome measures

Measure	Magnesium Group n=101 Participants Intravenous Magnesium Sulfate Intravenous Magnesium Sulfate: 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	Placebo Group n=103 Participants Normal Saline placebo Normal Saline Placebo: (1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses
Warm Sensation Associated With Study Drug Infusion	26 Participant	2 Participant

SECONDARY outcome

Timeframe: Rehospitalization will be measured at 7 days post discharge and at the follow-up visit (on average, 30 days post discharge)

Population: All participants who received at least one dose of study drug who had known rehospitalization status within 7 days

Outcome measures

Measure	Magnesium Group n=100 Participants Intravenous Magnesium Sulfate Intravenous Magnesium Sulfate: 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	Placebo Group n=102 Participants Normal Saline placebo Normal Saline Placebo: (1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses
Rehospitalization	12 Participant	7 Participant

SECONDARY outcome

Timeframe: Patients will be monitored daily, on average, during their length of stay until discharge, up to 10 days post enrollment

Outcome measures

Measure	Magnesium Group n=101 Participants Intravenous Magnesium Sulfate Intravenous Magnesium Sulfate: 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	Placebo Group n=103 Participants Normal Saline placebo Normal Saline Placebo: (1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses
Development of Acute Chest Syndrome (ACS)	16 Paricipants	14 Paricipants

SECONDARY outcome

Timeframe: Start of first study drug infusion to actual hospital discharge

Outcome measures

Measure	Magnesium Group n=100 Participants Intravenous Magnesium Sulfate Intravenous Magnesium Sulfate: 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	Placebo Group n=102 Participants Normal Saline placebo Normal Saline Placebo: (1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses
Hospital Length of Stay	74.5 Hours Interval 39.5 to 123.5	60.5 Hours Interval 37.0 to 122.0

Adverse Events

Magnesium Group

Serious events: 13 serious events

Other events: 66 other events

Deaths: 0 deaths

Placebo Group

Serious events: 12 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Measure	Magnesium Group n=101 participants at risk Intravenous Magnesium Sulfate Intravenous Magnesium Sulfate: 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	Placebo Group n=103 participants at risk Normal Saline placebo Normal Saline Placebo: (1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses
Blood and lymphatic system disorders Acute chest syndrome	9.9% 10/101 • Number of events 10 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	6.8% 7/103 • Number of events 7 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Hepatobiliary disorders Gallstones	0.99% 1/101 • Number of events 1 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	0.00% 0/103 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Infections and infestations Appendicitis	0.99% 1/101 • Number of events 1 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	0.00% 0/103 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Investigations Decreased hemoglobin	0.00% 0/101 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	3.9% 4/103 • Number of events 4 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.99% 1/101 • Number of events 1 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	0.00% 0/103 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/101 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	0.97% 1/103 • Number of events 1 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.

Other adverse events

Measure	Magnesium Group n=101 participants at risk Intravenous Magnesium Sulfate Intravenous Magnesium Sulfate: 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	Placebo Group n=103 participants at risk Normal Saline placebo Normal Saline Placebo: (1 ml/kg, max 60 ml), administered every 8 hours for a total of 6 doses
Blood and lymphatic system disorders Acute chest syndrome	5.9% 6/101 • Number of events 6 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	6.8% 7/103 • Number of events 7 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Blood and lymphatic system disorders Anemia	6.9% 7/101 • Number of events 7 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	6.8% 7/103 • Number of events 7 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Gastrointestinal disorders Constipation	7.9% 8/101 • Number of events 8 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	10.7% 11/103 • Number of events 11 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Gastrointestinal disorders Emesis	9.9% 10/101 • Number of events 10 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	8.7% 9/103 • Number of events 9 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Gastrointestinal disorders Nausea	15.8% 16/101 • Number of events 16 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	18.4% 19/103 • Number of events 20 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Gastrointestinal disorders Vomiting	5.0% 5/101 • Number of events 5 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	10.7% 11/103 • Number of events 11 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
General disorders Fever	26.7% 27/101 • Number of events 31 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	25.2% 26/103 • Number of events 26 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
General disorders Warmth	7.9% 8/101 • Number of events 10 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	0.00% 0/103 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Investigations Oxygen saturation decreased	7.9% 8/101 • Number of events 8 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	11.7% 12/103 • Number of events 12 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Nervous system disorders Dizziness	5.9% 6/101 • Number of events 7 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	3.9% 4/103 • Number of events 4 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Nervous system disorders Headache	11.9% 12/101 • Number of events 13 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	8.7% 9/103 • Number of events 11 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.99% 1/101 • Number of events 1 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	5.8% 6/103 • Number of events 6 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	6.9% 7/101 • Number of events 7 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	1.9% 2/103 • Number of events 2 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.
Skin and subcutaneous tissue disorders Itching	11.9% 12/101 • Number of events 12 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.	7.8% 8/103 • Number of events 8 Participant Flow and Baseline characteristics are reported for all randomized patients; however, adverse events only include the 204 (98%) who received study drug.

Additional Information

David Brousseau MD, MS

Medical College of Wisconsin

Phone: 414-266-2625

Email: dbrousse@mcw.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place