NCT02185885

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
197

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jul 2014

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2014

Completed
6 days until next milestone

First Submitted

Initial submission to the registry

July 7, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 10, 2014

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2016

Completed
Last Updated

April 11, 2016

Status Verified

April 1, 2016

Enrollment Period

1.5 years

First QC Date

July 7, 2014

Last Update Submit

April 8, 2016

Conditions

Embolic StrokePostoperative Cognitive Dysfunction

Keywords

Ischemic strokeEmbolic strokePostoperative Cognitive DysfunctionCardiac Bypass SurgeryCardiac Anaesthesia

Outcome Measures

Primary Outcomes (1)

  • Total volume of new ischemic cerebral lesions

    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.

    6 days

Secondary Outcomes (9)

  • Total number of new ischemic cerebral lesions

    6 days

  • Magnetic resonance spectroscopy - change from baseline N-acetylaspartate-creatine (NAA/Cr) ratio at day 6

    6 days

  • Magnetic resonance spectroscopy - change from baseline MRS Choline-creatine (Cho/Cr ratio) at day 6

    6 days

  • Postoperative cognitive dysfunction (POCD) - change from baseline neuropsychological test performance at day 5-8

    5-8 days

  • Postoperative cognitive dysfunction (POCD) - change from baseline neuropsychological test performance at 3 months

    3 months

  • +4 more secondary outcomes

Other Outcomes (1)

  • GAMPT BCC200 count

    End of cardiopulmonary bypass procedure

Study Arms (2)

Increased bloodpressure during CPB

EXPERIMENTAL

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.

Regular bloodpressure during CPB

NO INTERVENTION

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.

Interventions

Increased bloodpressure during CPB.PROCEDURE
Increased bloodpressure during CPB

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥ 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).

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

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

Copenhagen, DK-2100, Denmark

Location

Related Publications (7)

  • Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, van Beem H, Fraidakis O, Silverstein JH, Beneken JE, Gravenstein JS. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998 Mar 21;351(9106):857-61. doi: 10.1016/s0140-6736(97)07382-0.

    PMID: 9525362BACKGROUND

  • Vedel AG, Holmgaard F, Danielsen ER, Langkilde A, Paulson OB, Ravn HB, Rasmussen LS, Nilsson JC. Blood pressure and brain injury in cardiac surgery: a secondary analysis of a randomized trial. Eur J Cardiothorac Surg. 2020 Nov 1;58(5):1035-1044. doi: 10.1093/ejcts/ezaa216.

    PMID: 32840297DERIVED

  • Holmgaard F, Vedel AG, Rasmussen LS, Paulson OB, Nilsson JC, Ravn HB. The association between postoperative cognitive dysfunction and cerebral oximetry during cardiac surgery: a secondary analysis of a randomised trial. Br J Anaesth. 2019 Aug;123(2):196-205. doi: 10.1016/j.bja.2019.03.045. Epub 2019 May 17.

    PMID: 31104758DERIVED

  • Holmgaard F, Vedel AG, Lange T, Nilsson JC, Ravn HB. Impact of 2 Distinct Levels of Mean Arterial Pressure on Near-Infrared Spectroscopy During Cardiac Surgery: Secondary Outcome From a Randomized Clinical Trial. Anesth Analg. 2019 Jun;128(6):1081-1088. doi: 10.1213/ANE.0000000000003418.

    PMID: 31094772DERIVED

  • Holmgaard F, Vedel AG, Langkilde A, Lange T, Nilsson JC, Ravn HB. Differences in regional cerebral oximetry during cardiac surgery for patients with or without postoperative cerebral ischaemic lesions evaluated by magnetic resonance imaging. Br J Anaesth. 2018 Dec;121(6):1203-1211. doi: 10.1016/j.bja.2018.05.074. Epub 2018 Jul 26.

    PMID: 30442245DERIVED

  • Vedel AG, Holmgaard F, Rasmussen LS, Langkilde A, Paulson OB, Lange T, Thomsen C, Olsen PS, Ravn HB, Nilsson JC. High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients: A Randomized Controlled Trial. Circulation. 2018 Apr 24;137(17):1770-1780. doi: 10.1161/CIRCULATIONAHA.117.030308. Epub 2018 Jan 16.

    PMID: 29339351DERIVED

  • Vedel AG, Holmgaard F, Rasmussen LS, Paulson OB, Thomsen C, Danielsen ER, Langkilde A, Goetze JP, Lange T, Ravn HB, Nilsson JC. Perfusion Pressure Cerebral Infarct (PPCI) trial - the importance of mean arterial pressure during cardiopulmonary bypass to prevent cerebral complications after cardiac surgery: study protocol for a randomised controlled trial. Trials. 2016 May 17;17(1):247. doi: 10.1186/s13063-016-1373-6.

    PMID: 27189028DERIVED

MeSH Terms

Conditions

Embolic StrokePostoperative Cognitive ComplicationsIschemic Stroke

Condition Hierarchy (Ancestors)

StrokeCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesPostoperative ComplicationsPathologic ProcessesPathological Conditions, Signs and SymptomsCognitive DysfunctionCognition DisordersNeurocognitive DisordersMental Disorders

Study Officials

  • Jens C. Nilsson, MD, PhD

    Rigshospitalet, Denmark

    PRINCIPAL INVESTIGATOR

  • Hanne B. Ravn, MD, DMSc

    Rigshospitalet, Denmark

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Consultant, MD, PhD

Study Record Dates

First Submitted

July 7, 2014

First Posted

July 10, 2014

Study Start

July 1, 2014

Primary Completion

January 1, 2016

Study Completion

April 1, 2016

Last Updated

April 11, 2016

Record last verified: 2016-04

Locations

DK(1)