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HIgh Versus STAndard Blood Pressure Target in Hypertensive High-risk Patients Undergoing Major Abdominal Surgery (HISTAP)

Primary Purpose

Blood Pressure, Complication,Postoperative, Intraoperative Hypotension

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Ephedrine
Norepinephrine
Etilefrine Hydrochloride bolus
Use of pulse pressure and stroke volume variation (PPV and SVV); use of Mini Fluid Challenge (mini_FC)
Sponsored by
Humanitas Clinical and Research Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Blood Pressure focused on measuring Blood pressure, Intraoperative Hypotension, Postoperative complications, Postoperative mortality

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria (all the following) Adult patients ≥ 60 years History of chronic hypertension requiring home therapy. Scheduled for major elective abdominal surgery (laparoscopic, robotic or laparotomic) Expected surgical duration of at least 3 hours. Needing invasive arterial and hemodynamic monitoring as decided by the attending anesthetist, according to the rules of good clinical practice of each involved center. AND At increased risk of postoperative complications (at least one of the following): American Society of Anesthesiologists (ASA) class 3 or 4 Known or documented history of coronary artery disease (angina, myocardial infarction or acute coronary syndrome). Known or documented history of peripheral vascular disease. Known or documented history of heart failure requiring treatment. Ejection fraction less than 30% (echocardiography) Signs of diastolic moderate to severe dysfunction or chronic hypertensive cardiomyopathy (echocardiography) Moderate or severe valvular heart disease (echocardiography) Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) Radiographically confirmed or according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Diabetes currently treated with an oral hypoglycemic agent and/or insulin Morbid obesity (BMI ≥35 kg/m2) Preoperative serum albumin <30 g/l Anaerobic threshold (if done) <14 ml/kg/min Exercise tolerance equivalent to six metabolic equivalents (METs) or less as defined by American College of Cardiology/American Heart Association guidelines Exclusion criteria Refusal of consent Chronic kidney disease with glomerular filtration rate <30 ml/min/1.73 m2 or requiring renal-replacement therapy for end-stage renal disease Acute cardiovascular event, including acute or decompensated heart failure and acute coronary syndrome (within prior 30 days). Urgent or time-critical surgery Aortic or Renal vascular surgery (including nephrectomy) Liver Surgery Neurosurgery Surgery for palliative treatment only or ASA physical status 5 Pregnancy

Sites / Locations

  • Department of Anesthesia, Critical Care and Pain Medicine, SS. Annunziata Hospital
  • Department of Anesthesia and Intensive Care, University Hospital of Modena
  • Policlinico A. Gemelli
  • Humanitas Research HospitalRecruiting
  • Ospedali Riuniti Foggia- Università di FoggiaRecruiting
  • Fondazione Istituto San Raffaele G. GiglioRecruiting
  • Division of Anesthesia and Intensive Care, University of Messina, Policlinico "G. Martino"
  • Department of Surgical Oncological and Oral Science, University of Palermo
  • Careggi University HospitalRecruiting
  • Unit of Anesthesiology and Intensive Care B, Department of Surgery, Dentistry, Gynecology and Pediatrics, AOUI-University Hospital Integrated Trust of Verona

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

MAP 80

MAP 65

Arm Description

Intervention group: intraoperative mean blood pressure target > 80 mmHg. Treatment of hypotension (defined as a mean blood pressure of below 80 mmHg) using intravenous bolus or continuous infusion of vasopressors, or fluids using a dedicated algorithm considering the pulse pressure or stroke volume variation and the mini fluid challenge to optimize mean blood pressure values.

Control group: intraoperative mean blood pressure target > 65 mmHg. Treatment of hypotension (defined as a mean blood pressure of below 65 mmHg) using intravenous bolus or continuous infusion of vasopressors, or fluids using a dedicated algorithm considering the pulse pressure or stroke volume variation and the mini fluid challenge to optimize mean blood pressure values.

Outcomes

Primary Outcome Measures

Composite endpoint of postoperative mortality and at least one major organ dysfunction (see description in the secondary outcomes).
Composite postoperative outcome

Secondary Outcome Measures

Hospital stay (days)
Hospital stay (days)
ICU stay (days)
Intensive Care Unit stay (days)
ICU readmission
Intensive Care Unit readmissions
Sequential Organ Failure Assessment (SOFA) scores on postoperative
Postoperative organ failure - SOFA scores ranges from 0 (<2% of mortality) to 24 (>90% of mortality)
Overall intraoperative fluid balance
Intraoperative infusions (crystalloids, colloids, blood products) / Intraoperative loss balance (urine output)
Mortality
Mortality
Vasopressors use
Dose and timing of vasoactive drug infusion intraoperatively
Need for reoperation
Need of a new surgical treatment

Full Information

First Posted
November 24, 2022
Last Updated
September 26, 2023
Sponsor
Humanitas Clinical and Research Center
Collaborators
Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva
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1. Study Identification

Unique Protocol Identification Number
NCT05637606
Brief Title
HIgh Versus STAndard Blood Pressure Target in Hypertensive High-risk Patients Undergoing Major Abdominal Surgery
Acronym
HISTAP
Official Title
HIgh Versus STAndard Blood Pressure Target in Hypertensive High-risk Patients: The HISTAP Randomized Clinical Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 6, 2023 (Actual)
Primary Completion Date
March 1, 2024 (Anticipated)
Study Completion Date
September 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Humanitas Clinical and Research Center
Collaborators
Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is a multicenter randomized controlled trial comparing two strategies of mean arterial blood pressure management (MAP ≥ 80mmHg vs MAP ≥ 65 mmHg) in high-risk surgical patients undergoing elective laparotomic/laparoscopic surgery.
Detailed Description
Intraoperative hypotension has been associated with major postoperative complications after non-cardiac surgery. However, is is still unclear the optimal intraoperative mean arterial pressure (MAP) target in the subgroup of those patient with an history of hypertension at home, and at risk of developing postoperative complications. The objective of this study is to assess the effects of an intraoperative blood pressure management strategy aiming at keeping the MAP ≥ 80mmHg), as compared to the conventional practice (to maintain intraoperative MAP ≥ 65mmHg), on a composite outcome considering the death rate and the incidence of major events in patient scheduled for elective laparotomic/laparoscopic surgery. The primary outcome is a composite of 30-days from operation mortality rate and at least one major organ dysfunction including the renal, respiratory, cardiovascular and neurologic systems or new onset of sepsis and septic shock occurring by day 7 after surgery.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Blood Pressure, Complication,Postoperative, Intraoperative Hypotension
Keywords
Blood pressure, Intraoperative Hypotension, Postoperative complications, Postoperative mortality

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
The study will be a multicentric, randomized, non-blinded clinical trial. Eligible patients will be assigned in a 1:1 ratio to either a to control or treatment group. Randomization list will be created by a computer with the use of a permuted block design and embedded in the Electronic Case Report Form. Randomization will be performed using a 'block of 6" and stratified according to predefined baseline characteristics: Age ≥ 75 years Preoperative systolic pressure < 140 mmHg ≥ 140 mmHg
Masking
Outcomes Assessor
Masking Description
The trial intervention is not blinded for investigators, clinical staff, and patients, as blinding intraoperative MAP target is not feasible. The physicians of each center assessing all postoperative outcomes will be masked for the allocation.
Allocation
Randomized
Enrollment
636 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
MAP 80
Arm Type
Experimental
Arm Description
Intervention group: intraoperative mean blood pressure target > 80 mmHg. Treatment of hypotension (defined as a mean blood pressure of below 80 mmHg) using intravenous bolus or continuous infusion of vasopressors, or fluids using a dedicated algorithm considering the pulse pressure or stroke volume variation and the mini fluid challenge to optimize mean blood pressure values.
Arm Title
MAP 65
Arm Type
Other
Arm Description
Control group: intraoperative mean blood pressure target > 65 mmHg. Treatment of hypotension (defined as a mean blood pressure of below 65 mmHg) using intravenous bolus or continuous infusion of vasopressors, or fluids using a dedicated algorithm considering the pulse pressure or stroke volume variation and the mini fluid challenge to optimize mean blood pressure values.
Intervention Type
Drug
Intervention Name(s)
Ephedrine
Other Intervention Name(s)
Ephedrine bolus
Intervention Description
In both the group, the target MAP can be maintained by means of bolus of ephedrine (2.5 mg). The maximal dose for the ephedrine allowed is 25 mg (10 boluses of 2.5 mg), after this threshold a continuous infusion of norepinephrine will be started
Intervention Type
Drug
Intervention Name(s)
Norepinephrine
Other Intervention Name(s)
norepinephrine infusion
Intervention Description
In both the group, the target MAP can be maintained by means of bolus of ephedrine (2.5 mg) or Etilefrine (1 mg). The continuous infusion of norepinephrine, as decided by the attending anesthetist, may be started at any point of the intraoperative period. The starting dose of norepinephrine is the lowest needed to reach the predefined MAP target.
Intervention Type
Drug
Intervention Name(s)
Etilefrine Hydrochloride bolus
Intervention Description
The maximal dose for the etilefrine allowed is 10 mg (10 boluses of 1 mg), after this threshold a continuous infusion of norepinephrine will be started
Intervention Type
Diagnostic Test
Intervention Name(s)
Use of pulse pressure and stroke volume variation (PPV and SVV); use of Mini Fluid Challenge (mini_FC)
Other Intervention Name(s)
Hemodynamic optimization
Intervention Description
PPV, SVV and mini_FC will guide fluid bolus administration during an episode of intraoperative hypotension, following two predefined algorithms for laparotomic/non laparotomic surgery
Primary Outcome Measure Information:
Title
Composite endpoint of postoperative mortality and at least one major organ dysfunction (see description in the secondary outcomes).
Description
Composite postoperative outcome
Time Frame
up to 30 days after operation
Secondary Outcome Measure Information:
Title
Hospital stay (days)
Description
Hospital stay (days)
Time Frame
up to 30 days after operation
Title
ICU stay (days)
Description
Intensive Care Unit stay (days)
Time Frame
up to 30 days after operation
Title
ICU readmission
Description
Intensive Care Unit readmissions
Time Frame
up to 30 days after operation
Title
Sequential Organ Failure Assessment (SOFA) scores on postoperative
Description
Postoperative organ failure - SOFA scores ranges from 0 (<2% of mortality) to 24 (>90% of mortality)
Time Frame
up to 7 days after operation
Title
Overall intraoperative fluid balance
Description
Intraoperative infusions (crystalloids, colloids, blood products) / Intraoperative loss balance (urine output)
Time Frame
day 1 after the operation
Title
Mortality
Description
Mortality
Time Frame
up to 30 days after operation
Title
Vasopressors use
Description
Dose and timing of vasoactive drug infusion intraoperatively
Time Frame
day 1 after the operation
Title
Need for reoperation
Description
Need of a new surgical treatment
Time Frame
day 30 after operation
Other Pre-specified Outcome Measures:
Title
CARDIOVASCULAR complications
Description
Acute heart failure Myocardial injury after non-cardiac surgery Myocardial infarction Bradycardia Symptomatic proximal deep venous thrombosis Peripheral arterial and venous thrombosis
Time Frame
day 7 after operation
Title
NEUROLOGICAL complications
Description
Stroke Subarachnoid hemorrhage Cerebral venous thrombosis Seizure Acute delirium
Time Frame
day 7 after operation
Title
RESPIRATORY
Description
Acute respiratory distress Hypoxemia with or without acute respiratory distress Need for invasive, non-invasive ventilation or high-flow nasal cannula for acute respiratory distress. Acute respiratory distress syndrome. Pulmonary edema Pulmonary embolism
Time Frame
day 7 after operation
Title
RENAL
Description
• Acute Kidney Injury (AKI) and AKI stages defined according to the AKIN classification/staging system of acute kidney injury
Time Frame
day 7 after operation
Title
SEPSIS and Septic shock
Description
Based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria, sepsis required a quick Sequential Organ Failure Assessment (qSOFA) Score ≥ 2 points due to infection, septic shock defined as indicated by the Surviving Sepsis Campaign Guidelines
Time Frame
day 7 after operation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria (all the following) Adult patients ≥ 60 years History of chronic hypertension requiring home therapy. Scheduled for major elective abdominal surgery (laparoscopic, robotic or laparotomic) Expected surgical duration of at least 3 hours. Needing invasive arterial and hemodynamic monitoring as decided by the attending anesthetist, according to the rules of good clinical practice of each involved center. AND At increased risk of postoperative complications (at least one of the following): American Society of Anesthesiologists (ASA) class 3 or 4 Known or documented history of coronary artery disease (angina, myocardial infarction or acute coronary syndrome). Known or documented history of peripheral vascular disease. Known or documented history of heart failure requiring treatment. Ejection fraction less than 30% (echocardiography) Signs of diastolic moderate to severe dysfunction or chronic hypertensive cardiomyopathy (echocardiography) Moderate or severe valvular heart disease (echocardiography) Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) Radiographically confirmed or according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Diabetes currently treated with an oral hypoglycemic agent and/or insulin Morbid obesity (BMI ≥35 kg/m2) Preoperative serum albumin <30 g/l Anaerobic threshold (if done) <14 ml/kg/min Exercise tolerance equivalent to six metabolic equivalents (METs) or less as defined by American College of Cardiology/American Heart Association guidelines Exclusion criteria Refusal of consent Chronic kidney disease with glomerular filtration rate <30 ml/min/1.73 m2 or requiring renal-replacement therapy for end-stage renal disease Acute cardiovascular event, including acute or decompensated heart failure and acute coronary syndrome (within prior 30 days). Urgent or time-critical surgery Aortic or Renal vascular surgery (including nephrectomy) Liver Surgery Neurosurgery Surgery for palliative treatment only or ASA physical status 5 Pregnancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Antonio Messina
Phone
+390282241
Email
antonio.messina@humanitas.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Messina
Organizational Affiliation
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Anesthesia, Critical Care and Pain Medicine, SS. Annunziata Hospital
City
Chieti
State/Province
Abruzzo
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Salvatore Maurizio Maggiore
Facility Name
Department of Anesthesia and Intensive Care, University Hospital of Modena
City
Modena
State/Province
Emilia Romagna
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Massimo Girardis
Facility Name
Policlinico A. Gemelli
City
Roma
State/Province
Lazio
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Massimo Antonelli
Facility Name
Humanitas Research Hospital
City
Rozzano
State/Province
Milano
ZIP/Postal Code
20089
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Messina, PhD
Phone
0282241
Email
antonio.messina@humanitas.it
Facility Name
Ospedali Riuniti Foggia- Università di Foggia
City
Foggia
State/Province
Puglia
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lucia Mirabella
Email
lucia.mirabella@unifg.it
Facility Name
Fondazione Istituto San Raffaele G. Giglio
City
Cefalù
State/Province
Sicilia
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giovanni Misseri
Email
giovannimisseri1987@gmail.com
Facility Name
Division of Anesthesia and Intensive Care, University of Messina, Policlinico "G. Martino"
City
Messina
State/Province
Sicilia
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alberto Noto
Facility Name
Department of Surgical Oncological and Oral Science, University of Palermo
City
Palermo
State/Province
Sicilia
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Andrea Cortegiani
Facility Name
Careggi University Hospital
City
Firenze
State/Province
Toscana
ZIP/Postal Code
50134
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefano Romagnoli, MD
Facility Name
Unit of Anesthesiology and Intensive Care B, Department of Surgery, Dentistry, Gynecology and Pediatrics, AOUI-University Hospital Integrated Trust of Verona
City
Verona
State/Province
Veneto
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katia Donadello

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
33522953
Citation
Messina A, Robba C, Calabro L, Zambelli D, Iannuzzi F, Molinari E, Scarano S, Battaglini D, Baggiani M, De Mattei G, Saderi L, Sotgiu G, Pelosi P, Cecconi M. Association between perioperative fluid administration and postoperative outcomes: a 20-year systematic review and a meta-analysis of randomized goal-directed trials in major visceral/noncardiac surgery. Crit Care. 2021 Feb 1;25(1):43. doi: 10.1186/s13054-021-03464-1.
Results Reference
background
PubMed Identifier
23835589
Citation
Walsh M, Devereaux PJ, Garg AX, Kurz A, Turan A, Rodseth RN, Cywinski J, Thabane L, Sessler DI. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology. 2013 Sep;119(3):507-15. doi: 10.1097/ALN.0b013e3182a10e26.
Results Reference
background

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HIgh Versus STAndard Blood Pressure Target in Hypertensive High-risk Patients Undergoing Major Abdominal Surgery

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