Individuals Undergoing Cardiac and General Surgery
Conditions
Brief summary
The purpose of this study is to determine whether hydroxychloroquine decreases the relative leakage of the brain barrier after surgery.
Detailed description
Hydroxychloroquine will be administered preoperatively to 30 patients undergoing cardiac surgery. All patients will undergo magnetic resonance imaging (MRI) with gadolinium in the post-operative period before hospital discharge in order to assess blood-brain barrier permeability.
Interventions
DRUGHydroxychloroquine
Participants will be getting hydroxychloroquine
Sponsors
Duke University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, age ≥ 50 years old. 2. Patients scheduled to undergo cardiac surgery (CABG, CABG + Valve, Valve) with CPB. 3. Patient has voluntarily signed and dated the study-specific informed consent form approved by Duke University Health System Institutional Review Board (DUHS IRB)
Exclusion criteria
1. Cardiac surgery scheduled to be performed without cardiopulmonary bypass 2. Patients requiring emergent operation 3. Patients with a history of myocardial infarction within 7 days of surgery 4. Patients with a history of porphyria, psoriasis, chronic dermatitis, or retinal disease 5. Patients receiving preoperative digoxin 6. Patients with symptomatic cerebrovascular disease with substantial residual deficit 7. Patients with a history of alcohol abuse within 2 years of screening 8. Patients with a history of psychiatric illness and/or anxiety requiring medical treatment. 9. Patients with impaired liver and/or kidney functions (AST, ALT 2 times the upper limit of normal) 10. Patients with impaired renal functions (GFR \< 30ml/min) 11. Patients with less than a 7th-grade education or unable to read and thus unable complete the neuropsychological testing 12. Patients scoring \< 26 on a baseline Mini Mental State examination (MMSE) or scoring \>27 on the Center for Epidemiological Studies - Depression (CES-D) scale 13. Female subjects of childbearing potential who have had menstrual period within the past two years 14. Patients with bodily implants unsafe for MRI use 15. Patients with a history of claustrophobia 16. Known or suspected hypersensitivity to quinine (chloroquine or hydroxychloroquine) 17. Patient with pre-existing diagnosis of G6PD deficiency 18. Patients who have participated in another interventional clinical study within the previous 30 days 19. Any other concurrent disease or illness that, in the opinion of the investigator, makes the patient unsuitable for the study 20. Major ophthalmologic comorbidities (ex: ruptured globe, retinal vascular occlusive disease, retinal artery occlusion, anterior ischemic optic neuropathy, media opacification due to corneal abnormalities or cataract that prevent ocular and optical coherence tomography examination, glaucoma, age-related macular degeneration, history of intravitreal injections, and macular edema) 21. Patients who have received chemotherapy in the last 12 months 22. Patient with a QTc of 450 msec or greater (or 500 msec or greater in those with known IVCD, RBBB, or LBBB) at baseline will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ktrans Volume Transfer Constant | Postoperative day 1-5 | 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. |
Countries
United States
Participant flow
Recruitment details
Patients undergoing cardiac or noncardiac surgery were recruited at Duke University Medical Center.
Pre-assignment details
There was no enrollment in Phase 3, Phase 4, or Phase 5.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 8 |
| 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 | 8 |
| 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 | 0 |
| 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 | 0 |
| 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 | 0 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 3 | 3 | 0 | 0 | 0 |
| Overall Study | Unable to complete MRI | 2 | 2 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Phase 1 | Total | Phase 2 |
|---|---|---|---|
| Age, Continuous | 64.9 years STANDARD_DEVIATION 4.5 | 64.9 years STANDARD_DEVIATION 5.2 | 64.8 years STANDARD_DEVIATION 5.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 16 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 15 Participants | 7 Participants |
| Region of Enrollment United States | 8 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Female | 2 Participants | 6 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 10 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 3 / 12 | 3 / 12 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 12 | 1 / 12 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Ktrans Volume Transfer Constant
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.
Time frame: Postoperative day 1-5
Population: Participants who completed the MRI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1 | Ktrans Volume Transfer Constant | 0.225 unitless | Standard Deviation 0.108 |
| Phase 2 | Ktrans Volume Transfer Constant | 0.418 unitless | Standard Deviation 0.069 |