Clinical Trial Results:
Insulin Therapy for the Prevention of New Onset Diabetes after Transplantation (ITP-NODAT) Prospective Study in Non-Diabetic De Novo Kidney Transplant Recipients
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Summary
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EudraCT number |
2012-000225-51 |
Trial protocol |
ES AT |
Global end of trial date |
06 Aug 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Oct 2020
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First version publication date |
03 Oct 2020
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ITP-NODAT
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Medical University of Vienna
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Sponsor organisation address |
Währinger Gürtel 18-20, Vienna, Austria, 1090
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Public contact |
Manfred Hecking , Klinische Abteilung für Nephrologie und Dialyse, 0043 4040043901, manfred.hecking@meduniwien.ac.at
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Scientific contact |
Manfred Hecking, Klinische Abteilung für Nephrologie und Dialyse, 0043 4040043901, manfred.hecking@meduniwien.ac.at
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
23 May 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 May 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Aug 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
This study aims to assess the effects of early insulin therapy in previously non-diabetic de novo kidney transplant patients in reducing the incidence of new onset diabetes in particular and abnormal glucose metabolism in general during subsequent follow-up.
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Protection of trial subjects |
Personal information will be stored in a secure environment, and it will be transferred to the data coordinating center (DCC) using appropriate protections such as password protection and encryption. The study data will be maintained in a secure computer system with standard password protection accessible only to the investigators and dedicated study coordinator. The password will be updated on a quarterly basis. The leftover biological samples will be stored for future researches. Similarly, there is also a remote possibility of inappropriate sample handling. Precaution will be taken to prevent such improper handling: the research freezers are institutionally owned and securely locked with limited access to investigators and study coordinator, all samples are code identified and the link between code and patient’s identification will be maintained but stored separately in secured systems.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
04 Nov 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 74
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Country: Number of subjects enrolled |
Austria: 89
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Country: Number of subjects enrolled |
Germany: 100
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Worldwide total number of subjects |
263
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EEA total number of subjects |
263
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
215
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From 65 to 84 years |
48
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85 years and over |
0
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Recruitment
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Recruitment details |
All patients with end stage renal disease who have no history of diabetes and will undergo kidney transplantation from either a deceased or living donor at the participating transplant centers will be potential study participants. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Prior to transplantation, participants will be randomized into one of two study arms, A (intervention arm) and B (standard of care arm). A blocked randomization ratio of 1:1 will be performed at each transplant center. The only criteria for stratification will the number of previous transplant: first transplant versus repeat transplant. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall period
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
Blinding implementation details |
Single blind until month 3, afterwards unblinded
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Treatment | ||||||||||||||||||
Arm description |
Arm with early insulinization | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
Insulin Isophane Lispro
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
During the initial 4 weeks of capillary glucose monitoring, if patients have pre-dinner glucose levels of 140 mg/dl or greater, they will be started on insulin therapy with intermediate acting NPH insulin (human insulin isophane, Humulin N, Eli Lilly) in the morning before breakfast. The initial doses of NPH insulin are as following: 10 units before breakfast for pre-dinner capillary glucose levels between 140 and 179 mg/dl, 12 units between 180 and 239 mg/dl, and 14 units for 240 mg/dl and higher (Appendices, table 1). Once started on insulin therapy, 4 times daily capillary glucose monitoring will be continued. During therapy, the pre-dinner capillary glucose target is 110 mg/dl.
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Arm title
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Control | ||||||||||||||||||
Arm description |
Patients will be managed according to the current transplant centers practice with no routine glycemia monitoring other than once daily fasting glucose level in the morning as part of a basic metabolic panel to follow renal function improvement following the surgery. Patients whose glucose values are above 200 mg/dl will be monitored subsequently and, if confirmed, covered by short-acting insulin according to a sliding scale during their in-hospital stay. If a permanent antidiabetic medication is necessary, sulfonylureas will be the treatment of choice whenever possible. | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
Sulphonylurea
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Capillary blood glucose before meals and at bedtime (mg/dl)* Short-acting insulin dose (IU)**
351 and above 16
301 to 350 12
251 to 300 8
201 to 250 4
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Baseline characteristics reporting groups
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Reporting group title |
Treatment
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Reporting group description |
Arm with early insulinization | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control
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Reporting group description |
Patients will be managed according to the current transplant centers practice with no routine glycemia monitoring other than once daily fasting glucose level in the morning as part of a basic metabolic panel to follow renal function improvement following the surgery. Patients whose glucose values are above 200 mg/dl will be monitored subsequently and, if confirmed, covered by short-acting insulin according to a sliding scale during their in-hospital stay. If a permanent antidiabetic medication is necessary, sulfonylureas will be the treatment of choice whenever possible. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Treatment
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Treatment group in per protocol analysis
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Subject analysis set title |
Control
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Control group in per protocol analysis
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End points reporting groups
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Reporting group title |
Treatment
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Reporting group description |
Arm with early insulinization | ||
Reporting group title |
Control
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Reporting group description |
Patients will be managed according to the current transplant centers practice with no routine glycemia monitoring other than once daily fasting glucose level in the morning as part of a basic metabolic panel to follow renal function improvement following the surgery. Patients whose glucose values are above 200 mg/dl will be monitored subsequently and, if confirmed, covered by short-acting insulin according to a sliding scale during their in-hospital stay. If a permanent antidiabetic medication is necessary, sulfonylureas will be the treatment of choice whenever possible. | ||
Subject analysis set title |
Treatment
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Treatment group in per protocol analysis
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Subject analysis set title |
Control
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Control group in per protocol analysis
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End point title |
Incidence of Diabetes | |||||||||
End point description |
The incidence of NODAT 12 months after kidney transplantation defined according to American Diabetes Association criteria
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End point type |
Primary
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End point timeframe |
12 months
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Statistical analysis title |
Logistic Regression for primary Endpoint | |||||||||
Statistical analysis description |
We used logistic regression to estimate the odds for the requirement of antidiabetic medication or the development of PTDM in the treatment arm and in the control arm, adjusting for significant differences at baseline (polycystic kidney disease and glomerular disease).
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Comparison groups |
Treatment v Control
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Number of subjects included in analysis |
263
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Analysis specification |
Post-hoc
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Analysis type |
superiority [1] | |||||||||
P-value |
= 0.12 [2] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Confidence interval |
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| Notes [1] - Adjusted [2] - Adjusted Odds Ratio |
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Adverse events information
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Timeframe for reporting adverse events |
24 months
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.1
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Reporting groups
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Reporting group title |
Treatment
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Reporting group description |
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Reporting group title |
COntrol
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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06 Nov 2012 |
1. Role of the Sponsor: The Medical University of Vienna (MUV) is the sponsor of the multicentric ITP-NODAT Study in Europe. The reference to the National Institute of Diabetes, Digestive and Kidney Disease (NIDDK) was therefore omitted in the present version of the protocol.
2. Immunosuppression: Due to the transplant centers‘clinical practice in Europe, tacrolimus-based immunosuppression in Vienna, Graz, Berlin (both centres, namely Charité Campus Mitte and Charité Campus Virchow) as well as Barcelona will occur with once-daily tacrolimus (Advagraf by Astellas).
3. Data Recording and Data Administration: We will use paper-based Case Report Forms. Data entry into RedCap (as provided by the University of Michigan [U of M]) is optional (depending on the contracts agreed upon between U of M and MUV).
4. Serious Adverse Events (SAEs): Hopistalizations are the rule and not the exception after kidney transplantation. Because this study is not evaluating the role of transplantation as a risik factor (but instead is evaluationg a postoperative insulin intervention regimen), only those hospitalizations due to hypoglycemia (as well as hypoglycemias with blood glucose ≤40 mg/dL shall be judged as SAEs, in analogy to the NICE-SUGAR study (N Engl J Med. 2009 Mar 26;360(13):1283-97).
5. Monitoring: The Monitor for the ITP-NODAT study in European centers outside the MUV will be Carlos Rodriguez-Torres, DMD, MBA.
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12 Feb 2013 |
1. Immunsuppression: Es wurde das Cortison-Schema der Transplantationszentren in Europa an die derzeit in den meisten europäischen Zentren gängige Praxis angepasst (verringert).
2. Datenaufzeichnung und Datenverwaltung: Das Case Report Form wurde an das von der University of Michigan zur Verfügung gestellte RedCap angepasst.
3. Patienteninformation/Schwangerschaftstests: Nach Rücksprache und Einholung der Autorisierung durch Dr. Strasser (AGES) werden monatliche Schwangerschaftstests nur während der Dauer der Verabreichung der Studienmedilkation (Insulin) durchgeführt.
4. Monitoring: Der Monitor für die ITP-NODAT Studie -auch an der Medizinischen Universität Wien- ist Carlos Rodriguez-Torres, DMD, MBA.
5. Kontrolltermine in den Monaten 16 und 20. Diese Kontrolltermine werden nach Rücksprache mit den Investigatoren der University of Michigan weggelassen.
6. Die im Antragsformular fehlerhaft angekreuzte Indikationsstellung der Studienmedikation (Punkt 2.1.2) wurde korrigiert.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
