Diabetic Keto-acidosisPhase 4DRINKNCT06541535
Fluid Administration in Ketoacidosis (DRINK)
A Phase 4 study testing Fluid resuscitation with isotonic saline only and Fluid resuscitation with Ringer Lactate in people with Diabetic Keto-acidosis, run by Centre Hospitalier Universitaire de Nice at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Keto-acidosis
- What is being tested?
- Fluid resuscitation with isotonic saline only and Fluid resuscitation with Ringer Lactate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteFrance
- Study dates
- 26 Nov 2025to Jul 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Volume of fluid administered before inclusion <1L
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
CHU NICE
Nice
MATHIEU JOZWIAK, MD PhD, +33492035510, jozwiak.m@chu-nice.fr
About this study
Official title: Comparison of Saline and Ringer Lactate in Patients With Severe Diabetic Ketoacidosis (DRINK) : a Double-blind Randomized Controlled Trial
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
- Being tested
- Fluid resuscitation with isotonic saline only, Fluid resuscitation with Ringer Lactate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluid resuscitation with isotonic saline onlyDrug
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
Fluid resuscitation with Ringer LactateDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Isotonic saline | Active comparator | Not described Receives: Drug: Fluid resuscitation with isotonic saline only |
| Ringer Lactate | Experimental | Not described Receives: Drug: Fluid resuscitation with Ringer Lactate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 :
- capillary or blood glucose < 11 mmol/L
- undetectable ketonemia or ketonuria
- venous or arterial pH > 7.35 or venous or arterial bicarbonate > 20 mmol/L
Measured: at 24 hours
Secondary outcomes (7)
Speed of resolution of metabolic disorders
Compare fluid resuscitation with Ringer Lactate and isotonic saline solution on the speed of resolution of metabolic disorders in patients admitted to ICU for severe diabetic ketoacidosis.
Proportion of patients and number of hours ("Resolution free hours") within 48 hours of ICU admission with the following three criteria:
- capillary or blood glucose < 11 mmol/L
- undetectable ketonemia or ketonuria
- venous or arterial pH > 7.35 or venous or arterial bicarbonate > 20 mmol/L
Measured: at 48 hours
Time of resolution of metabolic disorders
Compare fluid resuscitation with Ringer Lactate and isotonic saline solution on the speed of resolution of metabolic disorders in patients admitted to ICU for severe diabetic ketoacidosis.
Time (in hours) from ICU admission to obtain one of the following three criteria:
- capillary or blood glucose < 11 mmol/L for at least 4 consecutive hours
- undetectable ketonemia or ketonuria
- venous or arterial pH > 7.35 or venous or arterial bicarbonate > 20 mmol/L
Measured: at 48 hours
Assess the metabolic tolerance of Ringer Lactate compared to isotonic saline solution
Assess the metabolic tolerance of Ringer Lactate compared to isotonic saline solution in patients admitted to ICU for severe diabetic ketoacidosis.
Occurrence of serious metabolic disorders during ICU stay, defined as :
- Kalemia < 3 mmol/L
- Natremia > 145 mmol/L
- Chloremia > 110 mmol/L
- Phosphoremia < 0.70 mmol/L
- Blood glucose < 3.8 mmol/L (i.e. 0.80 g/L)
- Persistent ketonemia/ketonuria 24 hours after ICU admission 2. Nature and volume (in liters) of fluid administered before inclusion and during the study period in each group 3. Protocol compliance (expressed as % of volume administered in each group)
Measured: through the end of study average 24 months
Assess the impact of Ringer lactate compared with isotonic saline on renal, neurological and cardiac complications
To assess the impact of Ringer lactate compared with isotonic saline on renal, neurological and cardiac complications during ICU stay and outcomes of patients admitted to ICU for severe diabetic ketoacidosis.
Occurrence of adverse events during ICU stay, defined as :
- Neurological disorders (Glasgow score)
- Acute renal failure (KDIGO classification)
- Cardiac disorders (supraventricular and ventricular rhythm disorders, acute coronary syndrome) 2. ICU and hospital length of stay 3. ICU mortality and Day-28 mortality
Measured: at 28 days
Assess the impact of Ringer lactate compared with isotonic saline on cardiac complications
To assess the impact of Ringer lactate compared with isotonic saline on cardiac complications during ICU stay and outcomes of patients admitted to ICU for severe diabetic ketoacidosis.
Occurrence of adverse events during ICU stay, defined as :
- Cardiac disorders (supraventricular and ventricular rhythm disorders, acute coronary syndrome)
- ICU and hospital length of stay
- ICU mortality and Day-28 mortality
Measured: at 28 days
Assess the impact of Ringer lactate compared with isotonic saline on renal complications
To assess the impact of Ringer lactate compared with isotonic saline on renal, complications during ICU stay and outcomes of patients admitted to ICU for severe diabetic ketoacidosis.
Measure acute renal failure with KDIGO classification.
The Kidney Disease: Improving Global Outcomes (KDIGO) classification system stratifies acute kidney injury (AKI) into levels of severity, determined by changes in serum creatinine (SCr) / estimated creatinine clearance (eCCl), as well as changes in urine output. The strata of severity of AKI can be reached by meeting the criteria for changes in SCr / eCCl or changes in urine output. There are three levels of severity, with level 1 being the least severe and level 3 the most severe.
No cut-off for the study
Measured: at 28 days
Assess the impact of Ringer lactate compared with isotonic saline on neurological complications
To assess the impact of Ringer lactate compared with isotonic saline on neurological complications during ICU stay and outcomes of patients admitted to ICU for severe diabetic ketoacidosis.
Measure Neurological disorders with Glasgow score. The Glasgow Coma Scale (GCS) is used to objectively describe the extent of impaired consciousness in all types of patients. The scale rates patients on three aspects of reactivity: eye opening, motor responses and verbal responses. It ranges from 3 (coma) to 15 (no disturbance of consciousness). No cut-off for the study.
Measured: at 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2024
- Study start26 Nov 2025
- Primary completionDec 2027 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Keto-acidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06541535
- Sponsor's protocol ID
- 22-API-03
- Acronym
- DRINK
- Status last verified
- May 2026
- First submitted
- 8 Jul 2024
- Last updated
- 26 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Saline and Ringer Lactate in Patients With Severe Diabetic Ketoacidosis (DRINK) : a Double-blind Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06541535
- Acronym / sponsor ID
- DRINK / 22-API-03
- Conditions
- Diabetic Keto-acidosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- 26 Nov 2025 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 7 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Isotonic saline | Active comparator | Drug: Fluid resuscitation with isotonic saline only |
| Ringer Lactate | Experimental | Drug: Fluid resuscitation with Ringer Lactate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- Patients <18 years
- Pregnant women
- Patients under protection
- Patients with a decision to withdraw life-sustaining therapy
- Contraindication to isotonic saline or Ringer Lactate
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fluid resuscitation with isotonic saline onlyIsotonic 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 | Drug | Isotonic saline |
| Fluid resuscitation with Ringer LactateRinger 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 | Drug | Ringer Lactate |
Primary outcome
Resolution of diabetic ketoacidosis
Time frame: at 24 hours
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
7 secondary outcomes
Speed of resolution of metabolic disorders
Time frame: at 48 hours
Time of resolution of metabolic disorders
Time frame: at 48 hours
Assess the metabolic tolerance of Ringer Lactate compared to isotonic saline solution
Time frame: through the end of study average 24 months
Assess the impact of Ringer lactate compared with isotonic saline on renal, neurological and cardiac complications
Time frame: at 28 days
Assess the impact of Ringer lactate compared with isotonic saline on cardiac complications
Time frame: at 28 days
Assess the impact of Ringer lactate compared with isotonic saline on renal complications
Time frame: at 28 days
Assess the impact of Ringer lactate compared with isotonic saline on neurological complications
Time frame: at 28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fluid resuscitation with isotonic saline only and Fluid resuscitation with Ringer Lactate in people with Diabetic Keto-acidosis, run by Centre Hospitalier Universitaire de Nice at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mathieu JOZWIAK, MD PhD (+33492035510, jozwiak.m@chu-nice.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resolution of diabetic ketoacidosis (time frame: at 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2026.