Fluid Administration in Ketoacidosis (DRINK)

NCT06541535 | Not Yet Recruiting Phase 4

• 1 other identifier: 22-API-03
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Management of severe diabetic ketoacidosis is based on insulin therapy, correction of metabolic disorders and fluid resuscitation. Current recommendations recommend the first-line use of isotonic saline, whose composition is unbalanced, rich in chloride and sodium compared with plasma. Administration of large volumes of isotonic saline is associated with a risk of hyperchloremic metabolic acidosis and acute renal failure. Balanced solutions (e.g. Ringer Lactate) are solutions with a more balanced electrolyte composition close to that of plasma. They could therefore enable diabetic ketoacidosis to be resolved more quickly than isotonic saline, due to a lower risk of hyperchloremic acidosis. Preliminary data suggest a potential benefit of balanced solutions for fluid resuscitation of patients with severe diabetic ketoacidosis in terms of resolution of diabetic ketoacidosis, but no randomized controlled double-blind study to date has compared balanced solution vs. isotonic saline in this context.

Conditions

Diabetic Keto-acidosis

Outcome Measures

Primary Outcomes (1)

• Resolution of diabetic ketoacidosis

  Compare fluid resuscitaiton with Ringer Lactate to isotonic saline on the resolution of diabetic ketoacidosis at 24 hours from admission to Intensive Care Unit (ICU) in patients with severe diabetic ketoacidosis. Resolution of ketoacidosis allowing discharge from ICU, defined as the proportion of patients with the following three criteria at 24 hours from ICU admission : 1. capillary or blood glucose \< 11 mmol/L 2. undetectable ketonemia or ketonuria 3. venous or arterial pH \> 7.35 or venous or arterial bicarbonate \> 20 mmol/L

  at 24 hours

Secondary Outcomes (7)

• Speed of resolution of metabolic disorders

  at 48 hours

• Time of resolution of metabolic disorders

  at 48 hours

• Assess the metabolic tolerance of Ringer Lactate compared to isotonic saline solution

  through the end of study average 24 months

• Assess the impact of Ringer lactate compared with isotonic saline on renal, neurological and cardiac complications

  at 28 days

• Assess the impact of Ringer lactate compared with isotonic saline on cardiac complications

  at 28 days

Study Arms (2)

Isotonic saline

ACTIVE COMPARATOR

Drug: Fluid resuscitation with isotonic saline only

Ringer Lactate

EXPERIMENTAL

Drug: Fluid resuscitation with Ringer Lactate

Interventions

Fluid resuscitation with isotonic saline only DRUG

Isotonic saline only will be used for fluid resuscitation in the first 48 hours of treatment, according to the protocol of English guidelines: * During the first hour of treatment: * In the event of systolic arterial hypotension (SAP\<90mmHg): administration of 500 mL over 15 minutes, renewable once, then administration of 1L over 1 hour. * In the absence of systolic arterial hypotension (SAP\>90mmHg): administration of 1L over 1 hour. * Between 60 minutes and 8 hours of treatment : * 1L over 2 hours, repeated once, then 1L over 4 hours * Adjust fluid resuscitation according to clinical tolerance * After the first 8 hours: * 1L over 4h then 1L over 6h * Clinical re-evaluation according to standard of care in participating centers

Isotonic saline

Fluid resuscitation with Ringer Lactate DRUG

Ringer Lactate only will be used for fluid resuscitation in the first 48 hours of treatment, according to the protocol of English guidelines: * During the first hour of treatment: * In the event of systolic arterial hypotension (SAP\<90mmHg): administration of 500 mL over 15 minutes, renewable once, then administration of 1L over 1 hour. * In the absence of systolic arterial hypotension (SAP\>90mmHg): administration of 1L over 1 hour. * Between 60 minutes and 8 hours of treatment : * 1L over 2 hours, repeated once, then 1L over 4 hours * Adjust fluid resuscitation according to clinical tolerance * After the first 8 hours: * 1L over 4h then 1L over 6h * Clinical re-evaluation according to standard of care in participating centers

Ringer Lactate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Admission to emergency department or direct admission to ICU
• Diagnosis of severe diabetic ketoacidosis requiring all the following criteria:
• Blood or capillary glucose \> 11 mmol/L
• Ketonemia or ketonuria \> 0
• Venous or arterial pH \< 7.30 or venous or arterial bicarbonate \< 15 mmol/L

You may not qualify if:

• Patients \<18 years
• Pregnant women
• Patients under protection
• Patients with a decision to withdraw life-sustaining therapy
• Contraindication to isotonic saline or Ringer Lactate
• Non-affiliation to social security

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (1)

CHU NICE

Nice, France

Location

MeSH Terms

Interventions

Ringer's Lactate

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Mathieu JOZWIAK, MD PhD

CONTACT

+33492035510; jozwiak.m@chu-nice.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: August 7, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 7, 2024

Record last verified: 2024-07

Locations

FR (1)