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

Sponsor
Humanitas Clinical and Research Center (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05637606
Collaborator
Società Italiana Anestesia, Analgesia, Rianimazione e Terapia Intensiva - SIAARTI (Other)
636
Enrollment
8
Locations
2
Arms
11.8
Anticipated Duration (Months)
79.5
Patients Per Site
6.8
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Ephedrine
  • Drug: Norepinephrine
  • Drug: Etilefrine Hydrochloride bolus
  • Diagnostic Test: Use of pulse pressure and stroke volume variation (PPV and SVV); use of Mini Fluid Challenge (mini_FC)
 N/A

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
636 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention 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 5" and stratified according to predefined baseline characteristics: Age ≥ 75 years Preoperative systolic pressure < 140 mmHg ≥ 140 mmHgThe 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 5" and stratified according to predefined baseline characteristics:Age ≥ 75 years Preoperative systolic pressure < 140 mmHg ≥ 140 mmHg
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
HIgh Versus STAndard Blood Pressure Target in Hypertensive High-risk Patients: The HISTAP Randomized Clinical Trial.
Anticipated Study Start Date :
Jan 8, 2023
Anticipated Primary Completion Date :
Sep 1, 2023
Anticipated Study Completion Date :
Jan 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: MAP 80

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.

Drug: Ephedrine
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
Other Names:
  • Ephedrine bolus

    • Drug: Norepinephrine
    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.
    Other Names:
  • norepinephrine infusion

    • Drug: Etilefrine Hydrochloride bolus
    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

    Diagnostic Test: Use of pulse pressure and stroke volume variation (PPV and SVV); use of Mini Fluid Challenge (mini_FC)
    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
    Other Names:
  • Hemodynamic optimization

    		•
    Other: MAP 65

    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.

    Drug: Ephedrine
    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
    Other Names:
  • Ephedrine bolus

    • Drug: Norepinephrine
    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.
    Other Names:
  • norepinephrine infusion

    • Drug: Etilefrine Hydrochloride bolus
    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

    Diagnostic Test: Use of pulse pressure and stroke volume variation (PPV and SVV); use of Mini Fluid Challenge (mini_FC)
    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
    Other Names:
  • Hemodynamic optimization

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Composite endpoint of postoperative mortality and at least one major organ dysfunction (see description in the secondary outcomes). [up to 30 days after operation]

      Composite postoperative outcome

    Secondary Outcome Measures

    1. Hospital stay (days) [up to 30 days after operation]

      Hospital stay (days)

    2. ICU stay (days) [up to 30 days after operation]

      Intensive Care Unit stay (days)

    3. ICU readmission [up to 30 days after operation]

      Intensive Care Unit readmissions

    4. Sequential Organ Failure Assessment (SOFA) scores on postoperative [up to 7 days after operation]

      Postoperative organ failure - SOFA scores ranges from 0 (<2% of mortality) to 24 (>90% of mortality)

    5. Overall intraoperative fluid balance [day 1 after the operation]

      Intraoperative infusions (crystalloids, colloids, blood products) / Intraoperative loss balance (urine output)

    6. Mortality [up to 30 days after operation]

      Mortality

    7. Vasopressors use [day 1 after the operation]

      Dose and timing of vasoactive drug infusion intraoperatively

    8. Need for reoperation [day 30 after operation]

      Need of a new surgical treatment

    Other Outcome Measures

    1. CARDIOVASCULAR complications [day 7 after operation]

      Acute heart failure Myocardial injury after non-cardiac surgery Myocardial infarction Bradycardia Symptomatic proximal deep venous thrombosis Peripheral arterial and venous thrombosis

    2. NEUROLOGICAL complications [day 7 after operation]

      Stroke Subarachnoid hemorrhage Cerebral venous thrombosis Seizure Acute delirium

    3. RESPIRATORY [day 7 after operation]

      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

    4. RENAL [day 7 after operation]

      • Acute Kidney Injury (AKI) and AKI stages defined according to the AKIN classification/staging system of acute kidney injury

    5. SEPSIS and Septic shock [day 7 after operation]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion criteria (all the following)

    1. Adult patients ≥ 60 years

    2. History of chronic hypertension requiring home therapy.

    3. Scheduled for major elective abdominal surgery (laparoscopic, robotic or laparotomic)

    4. Expected surgical duration of at least 3 hours.

    5. 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):

    1. American Society of Anesthesiologists (ASA) class 3 or 4

    2. Known or documented history of coronary artery disease (angina, myocardial infarction or acute coronary syndrome).

    3. Known or documented history of peripheral vascular disease.

    4. Known or documented history of heart failure requiring treatment.

    5. Ejection fraction less than 30% (echocardiography)

    6. Signs of diastolic moderate to severe dysfunction or chronic hypertensive cardiomyopathy (echocardiography)

    7. Moderate or severe valvular heart disease (echocardiography)

    8. Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) Radiographically confirmed or according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.

    9. Diabetes currently treated with an oral hypoglycemic agent and/or insulin

    10. Morbid obesity (BMI ≥35 kg/m2)

    11. Preoperative serum albumin <30 g/l

    12. Anaerobic threshold (if done) <14 ml/kg/min

    13. Exercise tolerance equivalent to six metabolic equivalents (METs) or less as defined by American College of Cardiology/American Heart Association guidelines

    Exclusion criteria

    1. Refusal of consent

    2. Chronic kidney disease with glomerular filtration rate <30 ml/min/1.73 m2 or requiring renal-replacement therapy for end-stage renal disease

    3. Acute cardiovascular event, including acute or decompensated heart failure and acute coronary syndrome (within prior 30 days).

    4. Urgent or time-critical surgery

    5. Aortic or Renal vascular surgery (including nephrectomy)

    6. Liver Surgery

    7. Neurosurgery

    8. Surgery for palliative treatment only or ASA physical status 5

    9. Pregnancy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Department of Anesthesia, Critical Care and Pain Medicine, SS. Annunziata Hospital Chieti Abruzzo Italy
    2 Department of Anesthesia and Intensive Care, University Hospital of Modena Modena Emilia Romagna Italy
    3 Policlinico A. Gemelli Roma Lazio Italy
    4 Humanitas Research Hospital Rozzano Milano Italy 20089
    5 Division of Anesthesia and Intensive Care, University of Messina, Policlinico "G. Martino" Messina Sicilia Italy
    6 Department of Surgical Oncological and Oral Science, University of Palermo Palermo Sicilia Italy
    7 Careggi University Hospital Firenze Toscana Italy 50134
    8 Unit of Anesthesiology and Intensive Care B, Department of Surgery, Dentistry, Gynecology and Pediatrics, AOUI-University Hospital Integrated Trust of Verona Verona Veneto Italy

    Sponsors and Collaborators

    • Humanitas Clinical and Research Center
    • Società Italiana Anestesia, Analgesia, Rianimazione e Terapia Intensiva - SIAARTI

    Investigators

    • Principal Investigator: Antonio Messina, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Antonio Messina, Principal Investigator, Humanitas Clinical and Research Center
    ClinicalTrials.gov Identifier:
    NCT05637606
    Other Study ID Numbers:
    • HISTAP TRIAL
    First Posted:
    Dec 5, 2022
    Last Update Posted:
    Dec 7, 2022
    Last Verified:
    Dec 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Antonio Messina, Principal Investigator, Humanitas Clinical and Research Center
    Blood pressure
    Intraoperative Hypotension
    Postoperative complications
    Postoperative mortality
    Additional relevant MeSH terms:
    Hypotension
    Postoperative Complications
    Etilefrine
    Norepinephrine
    Ephedrine
    Pseudoephedrine

    Study Results

    No Results Posted as of Dec 7, 2022