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Trial record 1 of 37 for:    PPCI Trial
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Perfusion Pressure Cerebral Infarction Trial (PPCI) (PPCI)

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ClinicalTrials.gov Identifier: NCT02185885
Recruitment Status : Completed
First Posted : July 10, 2014
Last Update Posted : April 11, 2016
Sponsor:
Collaborator:
Danish Heart Foundation
Information provided by (Responsible Party):
Jens C. Nilsson, Rigshospitalet, Denmark

Brief Summary:

STUDY HYPOTHESIS

In cardiac surgery the volume of perioperative cerebral infarctions can be reduced by increasing mean arterial pressure (MAP) during the cardiopulmonary bypass procedure.

BRIEF STUDY SUMMARY

Heart surgery using cardiopulmonary bypass (CPB) can be complicated by injury to the brain. Previous studies using brain scans have reported small stroke-like lesions in up to 51% of patients after cardiac surgery. However, only 1-6 % of patients have permanent symptoms of severe brain damage.

The majority of brain lesions seem to be caused by particulate matter (emboli) that wedge in blood vessels of the brain thereby compromising flow. In addition, insufficient blood flow to areas of the brain supplied by narrowed, calcified vessels may contribute. MAP during CPB usually stabilizes below the lower limit of cerebral autoregulation, which is accepted since sufficient total blood flow is guaranteed during CPB.

The aim of the PPCI trial is to investigate if increased MAP during CPB can prevent or reduce the extent of brain injury after cardiac surgery. A beneficial effect could result from reduced embolic injury through increased blood flow in collateral vessels and/or by increased blood flow in calcified arteries.

180 patients scheduled for cardiac surgery will be randomly allocated to increased MAP (70-80 mm Hg) or 'usual practice' (typically 45-50 mm Hg) during CPB, whereas CPB blood flow is intended equal and fixed in the two groups. Patients are examined before and 3-6 days after surgery with magnetic resonance imaging (MRI) brain scans, mental tests and by blood borne markers of brain injury.

If higher MAP during CPB is beneficial, a change of practice can easily be implemented in the clinical routine.


Condition or disease Intervention/treatment Phase
Embolic Stroke Postoperative Cognitive Dysfunction Procedure: Increased bloodpressure during CPB. Not Applicable

Detailed Description:

TRIAL DESIGN

The PPCI trial is a randomized, controlled, outcomes assessor and patient blinded, single-center superiority trial with two parallel groups in a 1:1 allocation ratio. The randomization will be stratified according to age (stratum 1 < 70 years; stratum 2 ≥ 70 years) and type of surgery (stratum 1 - surgery involving the aortic and/or mitral valve; stratum 2 - surgery not involving these valves).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 197 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Importance of Mean Arterial Pressure During Cardiopulmonary Bypass to Prevent Cerebral Complications After Cardiac Surgery - a Randomised Clinical Trial.
Study Start Date : July 2014
Actual Primary Completion Date : January 2016
Actual Study Completion Date : April 2016

Arm Intervention/treatment
Experimental: Increased bloodpressure during CPB
The cardiopulmonary bypass (CPB) procedure is conducted according to department guidelines with the modification that MAP is kept between 70 and 80 mm Hg. This is achieved by refract intravenous doses of phenylephrine to a total maximum of 2.0 mg, and after that continuous intravenous infusion of norepinephrine up to 0.4 μg/kg/min if necessary.
Procedure: Increased bloodpressure during CPB.
No Intervention: Regular bloodpressure during CPB
The cardiopulmonary bypass (CPB) procedure is conducted in accordance with departmental guidelines, where MAP is sought to be ≥ 45 mm Hg. This is achieved by refract intravenous doses of phenylephrine to a total maximum of 2.0 mg, and after that continuous intravenous infusion of norepinephrine up to 0.4 μg/kg/min if necessary.



Primary Outcome Measures :
  1. Total volume of new ischemic cerebral lesions [ Time Frame: 6 days ]

    The total volume of new ischemic cerebral lesions (sum in mL) assessed by diffusion-weighed-magnetic resonance imaging conducted preoperatively and again once postoperatively on day 3 to 6.

    The analysis will be adjusted for the randomization stratification variables age and type of surgery.



Secondary Outcome Measures :
  1. Total number of new ischemic cerebral lesions [ Time Frame: 6 days ]
    The total number of new ischemic cerebral lesions (sum in mL) assessed by diffusion-weighed-magnetic resonance imaging conducted preoperatively and again once postoperatively on day 3 to 6.

  2. Magnetic resonance spectroscopy - change from baseline N-acetylaspartate-creatine (NAA/Cr) ratio at day 6 [ Time Frame: 6 days ]
    Diffuse cerebral injury is investigated using Single-Voxel Magnetic Resonance Spectroscopy (MRS) in grey and white cerebral matter and expressed as the difference in N-acetylaspartate-creatine (NAA/Cr) ratio between a scan conducted preoperatively and one conducted postoperatively on day 3 to 6.

  3. Magnetic resonance spectroscopy - change from baseline MRS Choline-creatine (Cho/Cr ratio) at day 6 [ Time Frame: 6 days ]
    Diffuse cerebral injury is investigated using Single-Voxel Magnetic Resonance Spectroscopy (MRS) in grey and white cerebral matter and expressed as the difference in Choline-creatine (Cho/Cr ratio) between a scan conducted preoperatively and one conducted postoperatively on day 3 to 6.

  4. Postoperative cognitive dysfunction (POCD) - change from baseline neuropsychological test performance at day 5-8 [ Time Frame: 5-8 days ]

    The presence of cognitive dysfunction is evaluated preoperatively and on day 5-8 using the following collection of specific tests each time: "Visual Verbal Learning test", "Concept Shifting test", "Stroop Colour Word Interference test" and "Letter Digit Coding test".

    Cognitive dysfunction is defined as a deterioration corresponding to a Z-score > 2 (as defined by the ISPOCD group).


  5. Postoperative cognitive dysfunction (POCD) - change from baseline neuropsychological test performance at 3 months [ Time Frame: 3 months ]

    The presence of cognitive dysfunction is evaluated preoperatively and 3 months postoperatively using the following collection of specific tests each time: "Visual Verbal Learning test", "Concept Shifting test", "Stroop Colour Word Interference test" and "Letter Digit Coding test".

    Cognitive dysfunction is defined as a deterioration corresponding to a Z-score > 2 (as defined by the ISPOCD group).


  6. Peak value of biochemical markers of brain injury [ Time Frame: Prior to surgery on day 1 and 24 hours, 48 hours and 6 days after surgery ]
    Blood samples will be drawn at 4 different time points during the admission. Serum concentration and time course of the following markers of brain injury will be assessed: Phosphorylated Neurofilament Heavy Protein (pNfH), Glial Fibrillary Acidic Protein (GFAP), Matrix Metallopeptidase 9 (MMP-9) and Ubiquitin C-terminal Hydrolase 1 (UCH-L1).

  7. Near Infrared Spectroscopy (NIRS) - lowest value [ Time Frame: End of surgery ]
    Near Infrared Spectroscopy (NIRS) NIRS values from the right and left frontal lobes of the brain will be continuously monitored during the intraoperative period and saved for later analysis. The NIRS monitor will be hidden and muted during the procedure.

  8. Near Infrared Spectroscopy (NIRS) - total time below 25% of the baseline value on right and left side [ Time Frame: End of surgery ]
    Near Infrared Spectroscopy (NIRS) NIRS values from the right and left frontal lobes of the brain will be continuously monitored during the intraoperative period and saved for later analysis. The NIRS monitor will be hidden and muted during the procedure.

  9. Change from baseline performance at neurological examination day 6 [ Time Frame: 6 days ]
    New neurological deficits are assessed by performing an objective, clinical neurological examination.


Other Outcome Measures:
  1. GAMPT BCC200 count [ Time Frame: End of cardiopulmonary bypass procedure ]
    The GAMPT BCC200 is integrated into the heart-lung-machine (HLM), and through the use of ultrasound Doppler techniques, detection of gaseous micro-emboli (GME, volume between 5-500 µl) is enabled. The system can be used to quantify the GME that pass from the HLM into the bloodstream of the patient.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥ 18 years of age.
  • scheduled elective or subacute cardiac surgery with the use of CPB.
  • type of surgery either coronary artery bypass grafting (CABG) and/or heart valve surgery (provided that the valve prosthesis used is MRI compatible).

Exclusion Criteria:

  • a history of stroke.
  • a history of reversible ischemic deficits (duration of symptoms 24-72 hours)
  • a history of transitory ischemic attacks (duration of symptoms < 24 hours)
  • diagnosis of neurodegenerative disorders such as Alzheimers, Multiple Sclerosis etc.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02185885


Locations
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Denmark
Department of Cardiothoracic Surgery 2152 and Department of Cardiothoracic Anesthesiology 4142, Rigshospitalet / Copenhagen University Hospital
Copenhagen, Denmark, DK-2100
Sponsors and Collaborators
Rigshospitalet, Denmark
Danish Heart Foundation
Investigators
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Principal Investigator: Jens C. Nilsson, MD, PhD Rigshospitalet, Denmark
Study Chair: Hanne B. Ravn, MD, DMSc Rigshospitalet, Denmark
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Jens C. Nilsson, Consultant, MD, PhD, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT02185885    
Other Study ID Numbers: H-3-2013-110
E-22329-01 ( Other Identifier: Rigshospitalet, project.no. )
4142, PPCI ( Other Identifier: Dep. of Cardiothoracic Anesthesiology )
First Posted: July 10, 2014    Key Record Dates
Last Update Posted: April 11, 2016
Last Verified: April 2016
Keywords provided by Jens C. Nilsson, Rigshospitalet, Denmark:
Ischemic stroke
Embolic stroke
Postoperative Cognitive Dysfunction
Cardiac Bypass Surgery
Cardiac Anaesthesia
Additional relevant MeSH terms:
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Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders