TOnicity of Perioperative Maintenance SoluTions (TOPMAST-1)

TOnicity of Perioperative Maintenance SoluTions - Part 1: Thoracic Surgery

Prospective randomized double blind phase IV trial studying the efficacy and safety of the tonicity of two different perioperative maintenance solutions: an isotonic solution containing NaCl 0.9 in glucose 5% with an added 40 mmol/L of potassium or a commercially available premixed solution (Glucion 5%) containing a.o. 54 mmol/L of sodium and 26 mmol/L of potassium. Both solutions are administered at 27 mL/kg of ideal body weight, as recommended by current guidelines (NICE 174) and both solutions are widely used in daily clinical practice. The primary hypothesis is that isotonic maintenance solutions lead to more fluid retention than hypotonic fluids. Metabolism of both solutions is assessed by sequential analysis of urine and serum and clinical parameters.

Study Overview

• Status: Completed
• Conditions: Water-Electrolyte Imbalance; Fluid Overload; Thoracic Diseases; Fluid Retention; Sodium Disorder; Potassium Disorders; Chloride Disorder
• Intervention / Treatment: Drug: NaCl 0.9% in Glucose 5% + 40mmol/L Potassium; Drug: Glucion 5%

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • University Hospital, Antwerp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult (at least 18 y.o.)
• Undergoing elective lung resection (wedge resection, segmental resection, (bi)lobectomy, but not pneumonectomy) via thoracotomy or video- or robot assisted (VATS, RATS)
• Normal renal function (eGFR >60 ml/min/1.73m² (CKD-EPI))

Exclusion Criteria:

• Under chronic treatment with diuretics or desmopressin
• Heart failure (NYHA III-IV)
• Liver Failure
• Brittle diabetes mellitus
• Neurological contra-indication for hypotonic fluids
• SIADH or hyponatremia <130 or > 150 mmol/L at preoperative assessment
• Hyperkalemia > 5 mmol/L at preoperative assessment
• Under treatment with artificial nutrition (enteral or parenteral)
• Pregnancy

Additional pre-defined exclusion after initial inclusion

• Massive perioperative transfusion or intraoperative resuscitation of +2.5L of crystalloids/colloids
• Absence of admission to ICU

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NaCl 0.9% in Glucose 5% + 40mmol/L Potassium	Drug: NaCl 0.9% in Glucose 5% + 40mmol/L Potassium; Study fluid used at maintenance rate of 27 mmol per kg of body weight per day from beginning of surgery until end of study.
Active Comparator: Glucion 5%	Drug: Glucion 5%; Study fluid used at maintenance rate of 27 mmol per kg of body weight per day from beginning of surgery until end of study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluid balance	Difference between all fluid intake and output	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resuscitation Fluids	The cumulative amount of additional (resuscitation) fluids during the study period	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery)
Vasopressor Use	The cumulative amount of vasopressors during the study period	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery)
Physiological Mechanisms: Aldosterone level	Change from baseline aldosterone level at start of surgery	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) - Assessments at fixed time points.
Physiological Mechanisms: Fractional Excretion of Sodium	Change from baseline FeNa at start of surgery	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) - Assessments at fixed time points.
Electrolyte Homeostasis and Disorders: Sodium	Mean sodium level and change from baseline. Occurrence of hypo and hypernatremia.	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) - Assessments at fixed time points.
Electrolyte Homeostasis and Disorders: Potassium	Mean potassium level and change from baseline. Occurrence of hypo and hyperpotassemia.	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) - Assessments at fixed time points.
Electrolyte Homeostasis and Disorders: Chloride	Mean chloride level and change from baseline. Occurrence of hypo and hyperchloremia.	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) - Assessments at fixed time points.
Electrolyte Homeostasis and Disorders: Strong Ion Difference	Mean SID level and change from baseline.	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) - Assessments at fixed time points.
Electrolyte Homeostasis and Disorders: Phosphate	Mean phosphate level and change from baseline. Occurrence of hypo and hyperphosphatemia.	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) - Assessments at fixed time points.
Electrolyte Homeostasis and Disorders: Calcium	Mean calcium level and change from baseline. Occurrence of hypo and hypercalcemia.	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) - Assessments at fixed time points.
Clinical Endpoints: paO2/FiO2	Mean postoperative paO2/FiO2	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) - Assessments at fixed time points.
Clinical Endpoints: occurrence of de novo atrial fibrillation	occurrence of de novo atrial fibrillation (Y/N)	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery). Continuous assessment.
Clinical Endpoints: occurrence of acute kidney injury (AKI)	AKI according to RIFLE-score creatinine and urine R-I-F)	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery). Continuous assessment.
Sodium balance	Sodium balance (total in vs out) at end of study, assessed by urine collection.	From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery).

Collaborators and Investigators

• Sponsor: Niels Van Regenmortel

Publications and helpful links

General Publications

• Lobo DN, Bostock KA, Neal KR, Perkins AC, Rowlands BJ, Allison SP. Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial. Lancet. 2002 May 25;359(9320):1812-8. doi: 10.1016/S0140-6736(02)08711-1.
• Moritz ML, Ayus JC. Maintenance Intravenous Fluids in Acutely Ill Patients. N Engl J Med. 2015 Oct;373(14):1350-60. doi: 10.1056/NEJMra1412877. No abstract available.

Helpful Links

• NICE guideline on Intravenous Fluid Therapy in Adults in Hospital
• GIFTASUP guidelines

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2017
• Primary Completion (Actual): July 15, 2018
• Study Completion (Actual): July 15, 2018

Study Registration Dates

• First Submitted: February 19, 2017
• First Submitted That Met QC Criteria: March 9, 2017
• First Posted (Actual): March 15, 2017

Study Record Updates

• Last Update Posted (Actual): August 14, 2018
• Last Update Submitted That Met QC Criteria: August 10, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Maintenance Fluid Therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Respiratory Tract Diseases; Disease; Thoracic Diseases; Water-Electrolyte Imbalance
• Other Study ID Numbers: 17/4/34

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Anonymized data available on reasonable request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No