Trial Outcomes & Findings for Midodrine for the Treatment of Refractory Hypotension (NCT NCT01531959)

NCT ID: NCT01531959

Last Updated: 2020-10-28

Results Overview

Measured hours from initiation of midodrine until discontinuation of IV vasopressors

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 139 participants
• Primary outcome timeframe: From initiation of the study drug until discontinuation of IV vasopressors, assessed up to 400 hours
• Results posted on: 2020-10-28

Participant Flow

139 participants provided informed consent and were enrolled. 3 participants subsequently did no loner meet eligibility criteria and were therefore not randomized, resulting in a total number of started/randomized participants of 136.

Participant milestones

Measure	Midodrine Midodrine: Patients will be randomized to blinded to 20 mg of midodrine	Placebo Placebo: Patients will be randomized to blinded placebo control
Overall Study STARTED	68	68
Overall Study COMPLETED	66	66
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Midodrine for the Treatment of Refractory Hypotension

Baseline characteristics by cohort

Measure	Midodrine n=66 Participants Midodrine: Patients will be randomized to blinded to 20 mg of midodrine	Placebo n=66 Participants Placebo: Patients will be randomized to blinded placebo control	Total n=132 Participants Total of all reporting groups
Age, Continuous	70.0 years STANDARD_DEVIATION 12.6 • n=5 Participants	66.7 years STANDARD_DEVIATION 14.7 • n=7 Participants	68.4 years STANDARD_DEVIATION 13.7 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	34 Participants n=7 Participants	64 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	32 Participants n=7 Participants	68 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	64 Participants n=5 Participants	62 Participants n=7 Participants	126 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
APACHE II Score	14.7 units on a scale STANDARD_DEVIATION 5.2 • n=5 Participants	14.8 units on a scale STANDARD_DEVIATION 5.9 • n=7 Participants	14.7 units on a scale STANDARD_DEVIATION 5.5 • n=5 Participants
SOFA Score on admission day	4 units on a scale n=5 Participants	5 units on a scale n=7 Participants	4 units on a scale n=5 Participants
Body mass index	27.9 kg/m^2 STANDARD_DEVIATION 8.8 • n=5 Participants	29.8 kg/m^2 STANDARD_DEVIATION 8.8 • n=7 Participants	28.8 kg/m^2 STANDARD_DEVIATION 8.8 • n=5 Participants

PRIMARY outcome

Timeframe: From initiation of the study drug until discontinuation of IV vasopressors, assessed up to 400 hours

Measured hours from initiation of midodrine until discontinuation of IV vasopressors

Outcome measures

Measure	Midodrine n=66 Participants Midodrine: Patients will be randomized to blinded to 20 mg of midodrine	Placebo n=66 Participants Placebo: Patients will be randomized to blinded placebo control
Time Until Discontinuation of IV Vasopressors	23.5 hours Interval 10.0 to 54.0	22.5 hours Interval 10.4 to 40.0

SECONDARY outcome

Timeframe: From initiation of midodrine until ICU discharge, assessed up to 45 days

Measured number of days from initiation of midodrine until discharge ready from the ICU

Outcome measures

Measure	Midodrine n=66 Participants Midodrine: Patients will be randomized to blinded to 20 mg of midodrine	Placebo n=66 Participants Placebo: Patients will be randomized to blinded placebo control
ICU Length of Stay	6.0 days Interval 5.0 to 8.0	6.0 days Interval 4.0 to 8.0

SECONDARY outcome

Timeframe: From initiation of midodrine until hospital discharge, assessed up to 90 days

Measured number of days from initiation of midodrine until discharged from hospital

Outcome measures

Measure	Midodrine n=66 Participants Midodrine: Patients will be randomized to blinded to 20 mg of midodrine	Placebo n=66 Participants Placebo: Patients will be randomized to blinded placebo control
Hospital Length of Stay	11.0 days Interval 9.0 to 21.0	14.0 days Interval 9.0 to 22.0

SECONDARY outcome

Timeframe: Up to 2 months after ICU discharge

Number of patients initiated on midodrine that are readmitted back to ICU after being discharged to floor

Outcome measures

Measure	Midodrine n=66 Participants Midodrine: Patients will be randomized to blinded to 20 mg of midodrine	Placebo n=66 Participants Placebo: Patients will be randomized to blinded placebo control
Rates of ICU Readmission	1 Participants	3 Participants

SECONDARY outcome

Timeframe: From initiation of the study drug until discontinuation of the study drug, an average of 59 hours.

Measured rates of hypertension (increase in systolic blood pressure to values higher than those set by the primary team or greater than 160 mmg), bradycardia (decrease in heart rate to values lower than those set by the primary team or less than 40 BPM), hemodynamically significant tachyarrythmias (greater than 20 mmhg decrease in systolic blood pressure).

Outcome measures

Measure	Midodrine n=66 Participants Midodrine: Patients will be randomized to blinded to 20 mg of midodrine	Placebo n=66 Participants Placebo: Patients will be randomized to blinded placebo control
Rates of Hypertension, Bradycardia, and Hemodynamically Significant Tacharrythmias	12 Participants	3 Participants

Adverse Events

Midodrine

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 17 other events

Deaths: 1 deaths

Serious adverse events

Measure	Midodrine n=66 participants at risk Midodrine: Patients will be randomized to blinded to 20 mg of midodrine	Placebo n=66 participants at risk Placebo: Patients will be randomized to blinded placebo control
General disorders Death	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.

Other adverse events

Measure	Midodrine n=66 participants at risk Midodrine: Patients will be randomized to blinded to 20 mg of midodrine	Placebo n=66 participants at risk Placebo: Patients will be randomized to blinded placebo control
Cardiac disorders Hypertension	10.6% 7/66 • Number of events 7 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	4.5% 3/66 • Number of events 3 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Cardiac disorders Bradycardia	7.6% 5/66 • Number of events 5 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Cardiac disorders Atrial fibrillation	4.5% 3/66 • Number of events 3 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Gastrointestinal disorders Nausea	3.0% 2/66 • Number of events 2 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Investigations Lab parameter change	3.0% 2/66 • Number of events 2 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Renal and urinary disorders Urinary retention	3.0% 2/66 • Number of events 2 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Respiratory, thoracic and mediastinal disorders Cough/dyspnea	3.0% 2/66 • Number of events 2 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Nervous system disorders Paresthesia	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Psychiatric disorders Agitation	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	3.0% 2/66 • Number of events 2 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Cardiac disorders Myocardial infarction/ischemia	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Cardiac disorders Tachycardia	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
General disorders Peripheral edema	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Renal and urinary disorders Dysuria	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Nervous system disorders Lightheadedness	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Cardiac disorders Ventricular tachycardia	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Cardiac disorders Ventricular ectopic beats	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Nervous system disorders Subdural hemtoma	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Gastrointestinal disorders Small bowel obstruction	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Nervous system disorders Headache	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.
Skin and subcutaneous tissue disorders Rash	0.00% 0/66 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.	1.5% 1/66 • Number of events 1 • Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.

Additional Information

Matthias Eikermann

Beth Israel Deaconess Medical Center

Phone: 6176327034

Email: meikerma@bidmc.harvard.edu

Results disclosure agreements

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