Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001248459
Ethics application status
Approved
Date submitted
23/01/2015
Date registered
7/09/2016
Date last updated
7/09/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
The use of metformin in patients with moderate to severe renal failure and type 2 diabetes
Scientific title
A pharmacokinetic study of metformin in patients with stable stage 4 chronic kidney disease and type 2 diabetes
Secondary ID [1] 286011 0
Nil Known
Universal Trial Number (UTN)
U1111-1166-3205
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes mellitus 293973 0
Chronic Kidney Disease 293974 0
Condition category
Condition code
Metabolic and Endocrine 294274 294274 0 0
Diabetes
Renal and Urogenital 299916 299916 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention: Low dose metformin of 250mg, 500mg and 1000mg per day. Patients in cohort 1 will take 250mg dose. When this cohort has completed treatment cohort 2 will commence. Patients in cohort 2 will take a 500mg dose. After completion of cohort 2, patients in cohort 3 will commence and take the 1000mg dose.
Duration: 4 weeks
Method of administration: Oral
Adherence monitoring: Pill count and drug plasma level monitoring
Intervention code [1] 290990 0
Treatment: Drugs
Comparator / control treatment
Active
Participants to remain on current diabetic medication as per standard care
Control group
Active

Outcomes
Primary outcome [1] 294069 0
Trough metformin serum concentrations using high performance liquid chromatography (HPLC)
Timepoint [1] 294069 0
Weekly levels for 4 weeks
Secondary outcome [1] 312457 0
Single dose pharmacokinetic profile for metformin in patients with stage 4 chronic kidney disease using HPLC assay to measure serum metformin concentrations at 0, 2, 4, 6 ,8 and 24 hours.
Timepoint [1] 312457 0
Day 4 at 0, 2, 4, 6 ,8 and 24 hours.
Secondary outcome [2] 312458 0
72 hour continuous capillary glucose monitoring using an implanted Continuous Glucose Control Monitoring System (CGMS) with the sensor inserted subcutaneously into the abdominal wall.
Timepoint [2] 312458 0
Day 1-3 and Day 29-31
Secondary outcome [3] 312459 0
Hemoglobin A1c serum assay
Timepoint [3] 312459 0
Day 1 and Day 32
Secondary outcome [4] 312460 0
Serum lactate levels
Timepoint [4] 312460 0
Day 1, 11, 18, 25, 32
Secondary outcome [5] 312461 0
Serum bicarbonate levels
Timepoint [5] 312461 0
Day 1, 11, 18, 25, 32
Secondary outcome [6] 312462 0
Venous pH via venous blood gas
Timepoint [6] 312462 0
Day 1, 11, 18, 25, 32

Eligibility
Key inclusion criteria
1. Type 2 diabetes for at least 2 years
2. Haemoglobin A1c between 6 and 11%
3. Stable stage 4 chronic kidney disease as defined by estimated glomerular filtration rate of 15-29mls/1.73m2.
Minimum age
30 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Current treatment with metformin
2. Previous intolerance to metformin
3. Body mass greater than 160kg
4. Severe COPD as evidenced by hospitalization for decompensation within 6 months of randomization, chronic treatment with oral steroids
5. Unstable CHF needing frequent hospitalisations or frequent adjustment of heart failure medications
6. Significant IHD with acute coronary event, and/or CABG, and/or PCI in the previous 60 days.
7. Severe liver disease with icterus and plasma bilirubin greater than or equal to 60 micrommol/L, plasma transaminase greater than 3-fold upper limit of normal, albumin less than 25 g/L or coagulopathy.
8. Haemoglobin less tha 100 g/L or platelet count less than 80,000/mm3
9. Gastrointestinal bleeding in the previous 60 days
10. Unstable angina or planned for invasive cardiac investigations in the next 6 months
11. Malignancy other than basal cell carcinoma.
12. Any other disease or condition which in the opinion of the investigator could make them unsuitable for entry.
13. Pregnant, nursing a child, or planning a pregnancy at the time of this study

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
7/05/2012
Date of last participant enrolment
Anticipated
Actual
3/03/2014
Date of last data collection
Anticipated
Actual
3/04/2014
Sample size
Target
18
Accrual to date
Final
18
Recruitment outside Australia
Country [1] 6603 0
New Zealand
State/province [1] 6603 0

Funding & Sponsors
Funding source category [1] 290601 0
Charities/Societies/Foundations
Name [1] 290601 0
Middlemore Clinical Trials
Country [1] 290601 0
New Zealand
Primary sponsor type
Individual
Name
Dr Ajith Dissanayake
Address
Department of Medicine
Middlemore Hospital
Hospital Rd
Papatoetoe, Auckland 2025
Country
New Zealand
Secondary sponsor category [1] 289290 0
Individual
Name [1] 289290 0
Dr Christopher Hood
Address [1] 289290 0
Renal Department
Middlemore Hospital
Hospital Rd
Papatoetoe, Auckland 2025
Country [1] 289290 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292237 0
Northern X Regional Ethics Committee, Health and Disability Ethics Committees
Ethics committee address [1] 292237 0
Private Bag 92522
Wellesley Street
Auckland 1141
Ethics committee country [1] 292237 0
New Zealand
Date submitted for ethics approval [1] 292237 0
Approval date [1] 292237 0
19/12/2011
Ethics approval number [1] 292237 0
NTX/11/12/112

Summary
Brief summary
The primary goal of this study was to establish if treatment with low dose metformin in patients with stage 4 chronic kidney disease would produce safe and therapeutic serum levels of metformin. Metformin is widely acknowledged to be the first choice treatment for type 2 diabetes mellitus but fears around accumulation in patients with kidney disease have limited it's use in this patient group. Our aim is to investigate the use of low dose metformin in this group by showing predictable, stable and safe drug levels with low dose treatment.
Trial website
Trial related presentations / publications
Manuscript in preparation
Public notes

Contacts
Principal investigator
Name 54246 0
Dr Christopher Hood
Address 54246 0
Middlemore Hospital Private Bag 93311 Otahuhu Auckland 1640
Country 54246 0
New Zealand
Phone 54246 0
+64 9 276 0000
Fax 54246 0
Email 54246 0
[email protected]
Contact person for public queries
Name 54247 0
Dr Christopher Hood
Address 54247 0
Middlemore Hospital Private Bag 93311 Otahuhu Auckland 1640
Country 54247 0
New Zealand
Phone 54247 0
+64 9 276 0000
Fax 54247 0
Email 54247 0
[email protected]
Contact person for scientific queries
Name 54248 0
Dr Christopher Hood
Address 54248 0
Middlemore Hospital Private Bag 93311 Otahuhu Auckland 1640
Country 54248 0
New Zealand
Phone 54248 0
+64 9 276 0000
Fax 54248 0
Email 54248 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.