HyperglycemiaPhase 4NCT04284722
Perioperative Continuation of Metformin Therapy in Patients With Typ 2 Diabetes Mellitus Undergoing Non-cardiac Surgery
A Phase 4 study testing Metformin Hydrochloride in people with Hyperglycemia and Metformin, run by Kepler University Hospital.
Trial summary
Evaluation of the effect of peri-operative continuation of oral metformin therapy on the incidence of perioperative hyperglycemia compared to standard preoperative cessation of oral metformin therapy 24h before surgery. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Hyperglycemia, Metformin, Type 2 Diabetes
- What is being tested?
- Metformin Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- No sites listed yet
- Study dates
- Feb 2020to Apr 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-99 years
- Diabetes Mellitus Typ 2
- Oral metformin therapy
- Non cardiac-surgery
- Informed consent
Who cannot join
- Insulin therapy
- Ambulatory surgery
- Preoperative therapy with glucocorticoids (prednisolon or equivalent ≥ 5mg/day for more than 7 days)
- Planned postoperative ICU-stay
- Advanced renal insufficiency (eGFR < 45ml/kg/min)
- Advanced liver cirrhosis or failure (Child-Pugh B or C)
Show all 9Show fewer
- Alcohol abuse
- Pregnancy,
- Perioperative administration of contrast dye
Trial locations and contacts
No sites are listed yet.
About this study
Evaluation of the effect of peri-operative continuation of oral metformin therapy on the incidence of perioperative hyperglycemia compared to standard preoperative cessation of oral metformin therapy 24h before surgery.
Read the detailed description
Surgical procedures cause metabolic stress and can impair glucose control especially in patients with diabetes mellitus, which often results in peri-operative hyperglycemia. Peri-operative hyperglycemia is associated with impaired wound healing, secondary wound infections, endothelial dysfunction, sepsis, prolonged hospital stay and higher mortality.
Metformin is still the first line treatment in patients with type 2 diabetes mellitus.
Historically it has been stopped before surgery due to fear of hypoglycemia and metformin induced lactic acidosis. However recent studies have suggested that perioperative continuation of metformin might be safe and patients could benefit from more stable preoperative blood sugar levels.
Prospective studies evaluating the benefit of continuing oral metformin therapy in the perioperative period are rare.
The investigators plan to conduct a prospective, randomized-controlled, unblinded clinical trial where patients with type II diabetes mellitus and oral metformin therapy undergoing non-cardiac surgery will be randomized in either an interventional group or a control group. In the interventional group patients will be instructed to continue their regular metformin dose even on the day of surgery, in contrast to the control group, where the patients will be instructed to stop taking metformin 24h prior to surgery.
All other oral anti-diabetic drugs will be paused according to the local anesthesia guidelines.
The investigators plan to evaluate whether or not continuation of metformin can reduce the incidence of perioperative hyperglycemia and whether or not it is associated with elevation of blood lactate levels.
- Conditions
- Hyperglycemia, Metformin, Type 2 Diabetes, Hyperlactatemia
- Being tested
- Metformin Hydrochloride
- Medical subject headings
- Hyperglycemia, Diabetes Mellitus, Type 2, Hyperlactatemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin HydrochlorideDrug
Also called Group A
Perioperative continuation of oral metformin therapy according to the patient's normal dosage and dosage intervals
| Study group | Role | What they receive |
|---|---|---|
| Metformin + | Active comparator | The study intervention involves the self-administration of metformin in the same dosage as the patient's regular dosage according to regular dosing schedule and randomization. Receives: Drug: Metformin Hydrochloride |
| Metformin - | No intervention | The control group involves no intervention, which means cessation of oral metformin therapy 24 hours prior to surgery according to the local guidelines of the anesthesia department and the national anesthesiology guidelines. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Perioperative Hyperglycemia
blood glucose >180mg/dl (10mmol/l) and/or necessity of additive administration of insulin s.c. during the time frame
Measured: 24 hours pre-op until 24 hours post-op
Secondary outcomes (7)
Perioperative blood glucose control
mean plasma glucose at 4 defined dates: 24h pre-op, intra-op, 2hours post-op and 24h post-op
Measured: 24 hours pre-op until 24 hours post-op
Incidence hypoglycemia
blood sugar levels < 70mg/dl (3.9mmol/l)
Measured: 24 hours pre-op until 24 hours post-op
Perioperative lactate levels
mediane lactate levels at 4 defined dates: 24h pre-op, intra-op, 2 hours post-op and 24h post-op
Measured: 24 hours pre-op until 24 hours post-op
Incidence of hyperlactatemia
blood lactate values >4mmol/L at least at one of 4 measurement dates: 24h pre-op, intra-op, 2 hours post-op, 24 hours post-op
Measured: 24 hours pre-op until 24 hours post-op
Perioperative renal function
median serum-creatinine value at 24h pre-op and 24h post-op
Measured: 24 hours pre-op until 24 hours post-op
Hospitalization Duration
median time period from day of surgery until discharge from hospital
Measured: up to 4 weeks
Mortality
In-Hospital mortality
Measured: up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2020
- Study startFeb 2020 (estimated)
- Primary completionFeb 2021 (estimated)
- Study completionApr 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HyperglycemiaStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kepler University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jens Meier, Kepler University Hospital
- Investigators
- Jens Meier, MD, Principal investigator, Kepler University Hospital -Dpt. of Anesthesiology & Intensive Care Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04284722
- Sponsor's protocol ID
- 1126/2019
- Status last verified
- Feb 2020
- First submitted
- 20 Feb 2020
- Last updated
- 26 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hulst AH, Polderman JAW, Ouweneel E, Pijl AJ, Hollmann MW, DeVries JH, Preckel B, Hermanides J. Peri-operative continuation of metformin does not improve glycaemic control in patients with type 2 diabetes: A randomized controlled trial. Diabetes Obes Metab. 2018 Mar;20(3):749-752. doi: 10.1111/dom.13118. Epub 2017 Oct 13.
PubMed 28940961Gasanova I, Meng J, Minhajuddin A, Melikman E, Alexander JC, Joshi GP. Preoperative Continuation Versus Interruption of Oral Hypoglycemics in Type 2 Diabetic Patients Undergoing Ambulatory Surgery: A Randomized Controlled Trial. Anesth Analg. 2018 Oct;127(4):e54-e56. doi: 10.1213/ANE.0000000000003675.
PubMed 30044293Kuzulugil D, Papeix G, Luu J, Kerridge RK. Recent advances in diabetes treatments and their perioperative implications. Curr Opin Anaesthesiol. 2019 Jun;32(3):398-404. doi: 10.1097/ACO.0000000000000735.
PubMed 30958402Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev. 2010 Apr 14;2010(4):CD002967. doi: 10.1002/14651858.CD002967.pub4.
PubMed 20393934
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative Continuation of Metformin Therapy in Patients With Typ 2 Diabetes Mellitus Undergoing Non-cardiac Surgery
- ClinicalTrials.gov ID
- NCT04284722
- Acronym / sponsor ID
- 1126/2019
- Conditions
- Hyperglycemia, Metformin, Type 2 Diabetes, Hyperlactatemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Kepler University HospitalUniversity, hospital or other
- Study start
- Feb 2020 (estimated)
- Primary completion
- Feb 2021 (estimated)
- Study completion
- Apr 2021 (estimated)
- First posted
- 26 Feb 2020 (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.
Evaluation of the effect of peri-operative continuation of oral metformin therapy on the incidence of perioperative hyperglycemia compared to standard preoperative cessation of oral metformin therapy 24h before surgery.
Detailed description
Surgical procedures cause metabolic stress and can impair glucose control especially in patients with diabetes mellitus, which often results in peri-operative hyperglycemia. Peri-operative hyperglycemia is associated with impaired wound healing, secondary wound infections, endothelial dysfunction, sepsis, prolonged hospital stay and higher mortality.
Metformin is still the first line treatment in patients with type 2 diabetes mellitus.
Historically it has been stopped before surgery due to fear of hypoglycemia and metformin induced lactic acidosis. However recent studies have suggested that perioperative continuation of metformin might be safe and patients could benefit from more stable preoperative blood sugar levels.
Prospective studies evaluating the benefit of continuing oral metformin therapy in the perioperative period are rare.
The investigators plan to conduct a prospective, randomized-controlled, unblinded clinical trial where patients with type II diabetes mellitus and oral metformin therapy undergoing non-cardiac surgery will be randomized in either an interventional group or a control group. In the interventional group patients will be instructed to continue their regular metformin dose even on the day of surgery, in contrast to the control group, where the patients will be instructed to stop taking metformin 24h prior to surgery.
All other oral anti-diabetic drugs will be paused according to the local anesthesia guidelines.
The investigators plan to evaluate whether or not continuation of metformin can reduce the incidence of perioperative hyperglycemia and whether or not it is associated with elevation of blood lactate levels.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin + | Active comparator | Drug: Metformin HydrochlorideThe study intervention involves the self-administration of metformin in the same dosage as the patient's regular dosage according to regular dosing schedule and randomization. |
| Metformin - | No intervention | –The control group involves no intervention, which means cessation of oral metformin therapy 24 hours prior to surgery according to the local guidelines of the anesthesia department and the national anesthesiology guidelines. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18-99 years
- Diabetes Mellitus Typ 2
- Oral metformin therapy
- Non cardiac-surgery
- Informed consent
Key exclusion criteria (9 listed)
- Insulin therapy
- Ambulatory surgery
- Preoperative therapy with glucocorticoids (prednisolon or equivalent ≥ 5mg/day for more than 7 days)
- Planned postoperative ICU-stay
- Advanced renal insufficiency (eGFR < 45ml/kg/min)
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 |
|---|---|---|
| Metformin HydrochlorideAlso: Group APerioperative continuation of oral metformin therapy according to the patient's normal dosage and dosage intervals | Drug | Metformin + |
Primary outcome
Incidence of Perioperative Hyperglycemia
Time frame: 24 hours pre-op until 24 hours post-op
blood glucose >180mg/dl (10mmol/l) and/or necessity of additive administration of insulin s.c. during the time frame
7 secondary outcomes
Perioperative blood glucose control
Time frame: 24 hours pre-op until 24 hours post-op
Incidence hypoglycemia
Time frame: 24 hours pre-op until 24 hours post-op
Perioperative lactate levels
Time frame: 24 hours pre-op until 24 hours post-op
Incidence of hyperlactatemia
Time frame: 24 hours pre-op until 24 hours post-op
Perioperative renal function
Time frame: 24 hours pre-op until 24 hours post-op
Hospitalization Duration
Time frame: up to 4 weeks
Mortality
Time frame: up to 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2020.
- Background: PubMed 28940961Hulst AH, Polderman JAW, Ouweneel E, Pijl AJ, Hollmann MW, DeVries JH, Preckel B, Hermanides J. Peri-operative continuation of metformin does not improve glycaemic control in patients with type 2 diabetes: A randomized controlled trial. Diabetes Obes Metab. 2018 Mar;20(3):749-752. doi: 10.1111/dom.13118. Epub 2017 Oct 13.
- Background: PubMed 30044293Gasanova I, Meng J, Minhajuddin A, Melikman E, Alexander JC, Joshi GP. Preoperative Continuation Versus Interruption of Oral Hypoglycemics in Type 2 Diabetic Patients Undergoing Ambulatory Surgery: A Randomized Controlled Trial. Anesth Analg. 2018 Oct;127(4):e54-e56. doi: 10.1213/ANE.0000000000003675.
- Background: PubMed 30958402Kuzulugil D, Papeix G, Luu J, Kerridge RK. Recent advances in diabetes treatments and their perioperative implications. Curr Opin Anaesthesiol. 2019 Jun;32(3):398-404. doi: 10.1097/ACO.0000000000000735.
- Background: PubMed 20393934Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev. 2010 Apr 14;2010(4):CD002967. doi: 10.1002/14651858.CD002967.pub4.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Jens Meier, MD principal investigator
Kepler University Hospital -Dpt. of Anesthesiology & Intensive Care Medicine
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin Hydrochloride in people with Hyperglycemia and Metformin, run by Kepler University Hospital.
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 5 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 26 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Matthias Noitz, MD (+43 (0)5 7680 83 - 78171, matthias.noitz@kepleruniklinikum.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Perioperative Hyperglycemia (time frame: 24 hours pre-op until 24 hours post-op). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04284722, which also lists 4 linked publications.
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 Feb 2020.