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Completed

NCT Number: NCT02185885

Perfusion Pressure Cerebral Infarction Trial (PPCI)

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.

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Key information

Conditions

Embolic Stroke Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Cognition Disorders Cognitive Dysfunction Ischemic Stroke Mental Disorders Nervous System Diseases Neurocognitive Disorders Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Cognitive Complications Postoperative Cognitive Dysfunction Postoperative Complications Stroke Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Cardiothoracic Surgery 2152 and Department of Cardiothoracic Anesthesiology 4142, Rigshospitalet / Copenhagen University Hospital

Copenhagen, DK-2100, Denmark

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Increased bloodpressure during CPB.

Procedure

Primary outcomes

  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 outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Rigshospitalet, Denmark

Other

Collaborators

  • Danish Heart Foundation

Registry information

Official study title

The Importance of Mean Arterial Pressure During Cardiopulmonary Bypass to Prevent Cerebral Complications After Cardiac Surgery - a Randomised Clinical Trial.

Acronym: PPCI

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
Jul 10, 2014
Registry last updated
Apr 11, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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