Trial Outcomes & Findings for Hydroxychloroquine and Cognitive Function After Surgery (NCT NCT03025087)
NCT ID: NCT03025087
Last Updated: 2024-08-20
Results Overview
Ktrans represents the "permeability" or "leakage" constant across the blood-brain barrier and is calculated by measuring the amount of gadolinium-based contrast agent in the extravascular-extracellular space. Ktrans is a constant assessed on the postoperative MRI and has no units of measure.
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
24 participants
Primary outcome timeframe
Postoperative day 1-5
Results posted on
2024-08-20
Participant Flow
Patients undergoing cardiac or noncardiac surgery were recruited at Duke University Medical Center.
There was no enrollment in Phase 3, Phase 4, or Phase 5.
Participant milestones
| Measure |
Phase 1
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 2
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery followed by 400 mg daily until the day of MRI imaging on postoperative day 1-5
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 3
6 evaluable cardiac subjects 1000 mg HCQ on the day prior to surgery followed by 400 mg twice daily (800 mg total) until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 4
6 evaluable cardiac subjects: 1000 mg HCQ on the day prior to surgery followed by 500 mg twice daily (1000 mg total) until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 5
6 evaluable cardiac subjects: 1000 mg HCQ 1-2 hours after separation from CPB followed by the highest tolerated dose from the previous 4 phases divided into 2 equal daily doses until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
12
|
12
|
0
|
0
|
0
|
|
Overall Study
COMPLETED
|
6
|
6
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
6
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Phase 1
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 2
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery followed by 400 mg daily until the day of MRI imaging on postoperative day 1-5
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 3
6 evaluable cardiac subjects 1000 mg HCQ on the day prior to surgery followed by 400 mg twice daily (800 mg total) until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 4
6 evaluable cardiac subjects: 1000 mg HCQ on the day prior to surgery followed by 500 mg twice daily (1000 mg total) until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 5
6 evaluable cardiac subjects: 1000 mg HCQ 1-2 hours after separation from CPB followed by the highest tolerated dose from the previous 4 phases divided into 2 equal daily doses until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
|---|---|---|---|---|---|
|
Overall Study
Physician Decision
|
3
|
3
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
0
|
0
|
0
|
|
Overall Study
Unable to complete MRI
|
2
|
2
|
0
|
0
|
0
|
Baseline Characteristics
Hydroxychloroquine and Cognitive Function After Surgery
Baseline characteristics by cohort
| Measure |
Phase 1
n=8 Participants
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 2
n=8 Participants
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery followed by 400 mg daily until the day of MRI imaging on postoperative day 1-5
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 3
6 evaluable cardiac subjects 1000 mg HCQ on the day prior to surgery followed by 400 mg twice daily (800 mg total) until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 4
6 evaluable cardiac subjects: 1000 mg HCQ on the day prior to surgery followed by 500 mg twice daily (1000 mg total) until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 5
6 evaluable cardiac subjects: 1000 mg HCQ 1-2 hours after separation from CPB followed by the highest tolerated dose from the previous 4 phases divided into 2 equal daily doses until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
64.9 years
STANDARD_DEVIATION 4.5 • n=99 Participants
|
64.8 years
STANDARD_DEVIATION 5.8 • n=107 Participants
|
—
|
—
|
—
|
64.9 years
STANDARD_DEVIATION 5.2 • n=16 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
—
|
—
|
—
|
6 Participants
n=16 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
—
|
—
|
—
|
10 Participants
n=16 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
—
|
—
|
—
|
0 Participants
n=16 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
—
|
—
|
—
|
16 Participants
n=16 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
—
|
—
|
—
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
—
|
—
|
—
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
—
|
—
|
—
|
1 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
—
|
—
|
—
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
—
|
—
|
—
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
—
|
—
|
—
|
15 Participants
n=16 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
—
|
—
|
—
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
—
|
—
|
—
|
0 Participants
n=16 Participants
|
|
Region of Enrollment
United States
|
8 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
—
|
—
|
—
|
16 Participants
n=16 Participants
|
PRIMARY outcome
Timeframe: Postoperative day 1-5Population: Participants who completed the MRI.
Ktrans represents the "permeability" or "leakage" constant across the blood-brain barrier and is calculated by measuring the amount of gadolinium-based contrast agent in the extravascular-extracellular space. Ktrans is a constant assessed on the postoperative MRI and has no units of measure.
Outcome measures
| Measure |
Phase 1
n=4 Participants
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 2
n=4 Participants
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery followed by 400 mg daily until the day of MRI imaging on postoperative day 1-5
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
|---|---|---|
|
Ktrans Volume Transfer Constant
|
0.225 unitless
Standard Deviation 0.108
|
0.418 unitless
Standard Deviation 0.069
|
Adverse Events
Phase 1
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Phase 2
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Phase 3
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Phase 4
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Phase 5
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase 1
n=12 participants at risk
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 2
n=12 participants at risk
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery followed by 400 mg daily until the day of MRI imaging on postoperative day 1-5
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 3
6 evaluable cardiac subjects 1000 mg HCQ on the day prior to surgery followed by 400 mg twice daily (800 mg total) until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 4
6 evaluable cardiac subjects: 1000 mg HCQ on the day prior to surgery followed by 500 mg twice daily (1000 mg total) until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 5
6 evaluable cardiac subjects: 1000 mg HCQ 1-2 hours after separation from CPB followed by the highest tolerated dose from the previous 4 phases divided into 2 equal daily doses until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/12 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
8.3%
1/12 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
Other adverse events
| Measure |
Phase 1
n=12 participants at risk
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 2
n=12 participants at risk
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery followed by 400 mg daily until the day of MRI imaging on postoperative day 1-5
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 3
6 evaluable cardiac subjects 1000 mg HCQ on the day prior to surgery followed by 400 mg twice daily (800 mg total) until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 4
6 evaluable cardiac subjects: 1000 mg HCQ on the day prior to surgery followed by 500 mg twice daily (1000 mg total) until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
Phase 5
6 evaluable cardiac subjects: 1000 mg HCQ 1-2 hours after separation from CPB followed by the highest tolerated dose from the previous 4 phases divided into 2 equal daily doses until the day of MRI imaging on postoperative day 1-5.
Hydroxychloroquine: Participants will be getting hydroxychloroquine
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
0.00%
0/12 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
0.00%
0/12 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
|
Gastrointestinal disorders
Constipation
|
8.3%
1/12 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
0.00%
0/12 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
|
Gastrointestinal disorders
Ileus
|
8.3%
1/12 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
0.00%
0/12 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
|
Cardiac disorders
Hypotension
|
8.3%
1/12 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
8.3%
1/12 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/12 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
16.7%
2/12 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
—
0/0 • 6 weeks
No enrollment in Phase 3, Phase 4, or Phase 5.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place