E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fluid optimization has been considered as major contributor to improved oxygen delivery, and thus improved outcome in patients. Hypovolemia has been associated with significant increases in morbidity and mortality. Administering volume deliberately, however, also may have undesired effects like hemodynamic deterioration, pulmonary edema, tissue edema, and decreased O2-delivery. |
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E.1.1.1 | Medical condition in easily understood language |
Fluid optimization to improved oxygen delivery, and thus improved outcome in patients |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To test whether colloid-based goal-directed intraoperative fluid management leads to less perioperative morbidity compared to crystalloid-based goal-directed intraoperative fluid management.
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E.2.2 | Secondary objectives of the trial |
2. To compare colloid- vs. crystalloid-based goal-directed intraoperative fluid management on the outcome of various organ systems. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
After IRB approval and written informed consent patients aged 18 to 80 and scheduled for elective open abdominal surgery, open hysterectomy or myomectomy, or open urologic surgery (open prostatectomies and open cystectomies with ileal conduit formation) will be included in the study. Patients will be assigned to two groups: |
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E.4 | Principal exclusion criteria |
We will exclude patients having cardiac (EF<35%) or renal insufficiency (creatinine clearance < 30ml/min, or on renal replacement therapy), coronary (NYHA IV) or peripheral artery disease, COPD, coagulopathies, symptoms of infection or sepsis, or a history of susceptibility to malignant hyperthermia or porphyria. Participants in other studies will be excluded, when an interference of the studies cannot be ruled out. Operating Room records indicate that sufficient qualifying patients will be available to complete the proposed studies within the requested timetable. |
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E.5 End points |
E.5.1 | Primary end point(s) |
We will evaluate post-operative morbidity. This is the primary outcome parameter of the study and will define the stopping point of the study. Postoperative morbidity will be assessed daily with a postoperative morbidity survey [40] by a team member strictly blinded to group assignment. We add mortality end rehospitalization within 30 postoperative days. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Subcutaneous oxygen tension (PsqO2) will be evaluated intraoperatively in a subgroup of 60 patients with a polarographic-type tissue oxygen sensor (Licox, Inc. Germany) positioned within a subcutaneous, saline filled Silastic® tonometer inserted into the patients’ upper arm after induction of anesthesia. (Silastic® readily permits transfer of oxygen by diffusion.) It has been shown previously, that subcutaneous oxygen tension in the upper arm is comparable to oxygen tension at the side of chest and abdominal wounds though it is about 10 mmHg higher than in the incised wound [41]. The arm is chosen, because it is convenient and can be accessed intraoperatively.
The tonometer consists of a Luer-hubbed, 15-cm-long segment of Silastic® tubing (internal diameter, 0,8 mm; external diameter, 1.0 mm). Under controlled conditions, the optode measures p02 accurately and reliably in vitro over a broad range of p02 values and temperatures. In vitro accuracy of the optode (in a water bath at 37 C) is ± 3 mmHg for the range from 0-100 mmHg, and ± 5% for the range 100-360 mmHg. Temperature sensitivity is 0.25%/°C, but a thermistor is incorporated into the probe and temperature-compensation is included in the PsqO2 calculation. The calibration remains stable (within 8% of baseline value for room air) in vitro for at least 72 hours and in vivo for at least 8 hours. The polographic sensor will be initially calibrated, as in our previous studies, by exposing it to room air (pO2=154 mmHg). It will then be inserted into the Silastic® tonometer, which will be flushed with hypoxic saline to provide more rapid equilibration with the surrounding tissue. The optode will be allowed to equilibrate with tissue oxygen for at least 30 minutes. It was shown that this time period is sufficient for any clinically observed PsqO2. It also was shown that PsqO2 values correlate well with the incidence of clinically significant wound infections. Measurements will start as soon as practical after induction of anesthesia. Values will be recorded at 10-minute intervals during surgery as well as during the first two hours of recovery, and on the first postoperative day, respectively. The silastic tonometer will be removed immediately after the investigation period. As the tissue of interest for colon surgery is the gut we will measure intramural intestinal oxygen partial pressure (PimO2) intraoperatively. Surgeons will insert oxygen sensors through 20-g-cannulae into a section of the descending colon(approximately 20 cm away from the tumor) that will subsequently be resected. The probes will be inserted into the tissue plane between the serosa and mucosa after mobilization of the left colon. Additionally, needle temperature probes will be inserted adjacent to the oxygen probes(Tyco-mallinckrodt Anesthesiology Products). In order to obtain temperature corrected measurements, we will adjust the Licox monitor according to the measured temperature. PimO2 will be measured every 60 seconds for fifteen minutes, surgery will be discontinued during PimO2 measurements. At the end of surgery, a tonometer will be inserted 2-3 cm lateral and parallel to the surgical incision to measure wound tissue oxygen tension (PsqO2 wound) 2 hours postoperatively every ten minutes.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 9 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 9 |