Acute Kidney Insufficiency, Kidney Failure, Acute
Conditions
Keywords
renal, kidney, injury, acute, bypass, cardiac, minocycline, prevention, Acute Kidney Failure
Brief summary
This study proposes to investigate whether treatment with minocycline pre-operatively in patients with mild to moderate chronic kidney disease undergoing cardiac surgery will reduce the occurence of kidney injury.
Interventions
DRUGminocycline
given at least for 4 doses (200mg initially then 100mg every 12 hours until surgery)with maximum of 14 doses
DRUGplacebo
placebo will be given for at least 4 doses pre-op to a maximum of 14 doses
Sponsors
Satellite Healthcare
Triax Pharmaceuticals
Tarek M. El-Achkar
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Age over 18 years * planned CABG or valvular surgery with cardiopulmonary bypass * Serum creatinine available (within 30 days) * Estimated GFR 15-90ml/min using the abbreviated MDRD formula (CKD stages 2-4)
Exclusion criteria
* Emergent or urgent surgery (to be performed within the next 36 hours) * End stage renal disease, or GFR \< 15ml/min (CKD stage 5) * Estimated GFR\>90ml/min (CKD stage 1 or no CKD) * Ongoing infection by positive blood, urine or sputum cultures or pneumonia on CXR * Allergy to minocycline or tetracyclines * inability to take oral medications * use of preoperative vasopressor agents at therapeutic doses * Pregnant or lactating females * Advanced liver disease by history or exam(cirrhosis, ascitis, jaundice) * Rising creatinine meeting the definition of acute kidney injury prior to surgery * Neurologic signs or symptoms or history of increased intracranial pressure * current participation in another research study involving an investigational drug or device
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Development of Post-operative Acute Kidney Injury | up to 5 days post cardiac surgery | Participants who develop a Creatinine increase by 0.3 mg/dl (AKIN definition) in any 48 hours time period, within 5 days post-operatively |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post Operative Hospital Days | 30 days post-operative | — |
| On Vent >48 Hours | 30 days post op | on ventilator \> 48 hours |
| Infections Post Operative | 30 days post operative | — |
| Stroke Post Operative | 30 days post op | — |
| Re-operation | 30 days post-operative | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Minocycline minocycline: given at least for 4 doses (200mg initially then 100mg every 12 hours until surgery)with maximum of 14 doses | 20 |
| Placebo placebo: placebo will be given for at least 4 doses pre-op to a maximum of 14 doses | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Minocycline | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 18 Participants | 36 Participants |
| Age, Continuous | 64.1 years STANDARD_DEVIATION 9.9 | 60.8 years STANDARD_DEVIATION 11.5 | 62 years STANDARD_DEVIATION 10.4 |
| kidney function | 71.9 ml/min STANDARD_DEVIATION 26.4 | 77.3 ml/min STANDARD_DEVIATION 27.4 | 74.3 ml/min STANDARD_DEVIATION 26.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 7 Participants | 14 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 | 13 Participants | 13 Participants | 26 Participants |
| Region of Enrollment United States | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 16 Participants | 17 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 19 | 0 / 19 |
| serious Total, serious adverse events | 4 / 19 | 3 / 19 |
Outcome results
Primary
Development of Post-operative Acute Kidney Injury
Participants who develop a Creatinine increase by 0.3 mg/dl (AKIN definition) in any 48 hours time period, within 5 days post-operatively
Time frame: up to 5 days post cardiac surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Minocycline | Development of Post-operative Acute Kidney Injury | 10 participants meeting primary oputcome |
| Placebo | Development of Post-operative Acute Kidney Injury | 7 participants meeting primary oputcome |
Secondary
Infections Post Operative
Time frame: 30 days post operative
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Minocycline | Infections Post Operative | 2 Participants |
| Placebo | Infections Post Operative | 3 Participants |
Secondary
On Vent >48 Hours
on ventilator \> 48 hours
Time frame: 30 days post op
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Minocycline | On Vent >48 Hours | 15.8 percentage of participant per group |
| Placebo | On Vent >48 Hours | 26.3 percentage of participant per group |
Secondary
Post Operative Hospital Days
Time frame: 30 days post-operative
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Post Operative Hospital Days | 8.7 days | Standard Error 3.8 |
| Placebo | Post Operative Hospital Days | 9.8 days | Standard Error 7.2 |
Secondary
Re-operation
Time frame: 30 days post-operative
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Minocycline | Re-operation | 2 Participants |
| Placebo | Re-operation | 1 Participants |
Secondary
Stroke Post Operative
Time frame: 30 days post op
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Minocycline | Stroke Post Operative | 2 Participants |
| Placebo | Stroke Post Operative | 0 Participants |