Ignite Creation Date:
2024-05-05 @ 12:05 PM
Last Modification Date:
2024-10-26 @ 9:20 AM
Study NCT ID:
NCT00237549
Status:
COMPLETED
Last Update Posted:
2013-12-20
First Post:
2005-10-10
Brief Title:
The ADDITION Study Intensive Treatment in People With Screen Detected Diabetes in Primary Care
Sponsor:
University of Aarhus
Organization:
University of Aarhus
Study Overview
Official Title:
The ADDITION Study Anglo-Danish-Dutch Study of Intensive Treatment In PeOple With screeN Detected Diabetes in Primary Care
Status:
COMPLETED
Status Verified Date:
2012-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ADDTION
Brief Summary:
The ADDITION study comprise 2 parts screening for Type 2 diabetes and intensive treatment compared to standard treatment
1 In the screening study the feasibility and results of country specific models to identify undiagnosed individuals with Type 2 diabetes will be evaluated
2 In the treatment study the effects of routine care in general practice according to local and national guidelines will be compared with an intensive ADDITION protocol including structured lifestyle education dietary modification increased physical activity and smoking cessation and intensive treatment of blood glucose blood pressure and lipids and prophylactic aspirin with or without motivational interviewing on mortality macrovascular and microvascular disease Furthermore the impact of treatment on health status treatment satisfaction and health service costs will also be assessed
1 In the screening study the feasibility and results of country specific models to identify undiagnosed individuals with Type 2 diabetes will be evaluated
2 In the treatment study the effects of routine care in general practice according to local and national guidelines will be compared with an intensive ADDITION protocol including structured lifestyle education dietary modification increased physical activity and smoking cessation and intensive treatment of blood glucose blood pressure and lipids and prophylactic aspirin with or without motivational interviewing on mortality macrovascular and microvascular disease Furthermore the impact of treatment on health status treatment satisfaction and health service costs will also be assessed
Detailed Description:
Aims
To develop and evaluate strategies for early detection of type 2 diabetes in different countries and different populations
To study whether a multifactorial treatment strategy can reduce CVD-mortality and reduce the incidence of macro- and microvascular complications The treatment strategy consists of motivational interviewing encouraging behavioural changes dietary advises physical activity smoking cessation and intensive pharmacological treatment of blood pressure blood glucose and serum lipids
To identify genetic markers predicting development of diabetic complications
To evaluate health economical consequences of screening and early intervention for type 2 diabetes
Design and methods
The study is an investigator initiated and designed study initiated in Denmark by the two principal investigators planned and conducted in collaboration between the four centers in Denmark UK and the Netherlands The study has two elements a screening study and a subsequent intervention study
In the screening study the feasibility and results of country specific models to identify undiagnosed individuals with Type 2 diabetes will be evaluated
In the treatment study the effects of routine care in general practice according to local and national guidelines will be compared with an intensive ADDITION protocol including structured lifestyle education dietary modification increased physical activity and smoking cessation and intensive treatment of blood glucose blood pressure and lipids and prophylactic aspirin with or without motivational interviewing on mortality macrovascular and microvascular disease Furthermore the impact of treatment on health status treatment satisfaction and health service costs will also be assessed
Methodology - Screening study
In Denmark 300 primary care physicians from 5 different counties Copenhagen Aarhus Ringkøbing Ribe and Sønderjylland participate in the study Diabetes-related information is sent to all individuals aged 40-69 years enrolled in their practice A questionnaire diabetes risk score29 including age gender family history of type 2 diabetes obesity physical activity and previously diagnosed hypertension was used Individuals scoring high on the questionnaire are encouraged to contact their physician for an examination of random blood glucose RGB and HbA1c A step-wise strategy based on RBG HbA1c FPG and OGTT is used to diagnose diabetes In the Netherlands all people aged 50-69 years and listed with the participating primary care physicians is invited to fill in a diabetes risk questionnaire based on the same risk factors as in Denmark Those at high risk of having type 2 diabetes are requested to come for a screening visit at a centre set up near the general practice A stepwise screening strategy based on RBG FPG and OGTT is used to diagnose diabetes In UK different strategies are used in Cambridgeshire and Leicester In Cambridgeshire a search of computerised general practice records is performed using a simple validated risk score based on routine general practice data age gender prescribed medication and body mass index to identify people in the age of 40-69 years at high risk of having undiagnosed diabetes30 Those with a high score undergo a stepwise screening strategy based on RBG FPG and OGTT is used to diagnose diabetes In Leicester all white European subjects aged 40-75 years and Asian black or Chinese subjects aged 25-75 years are invited in a restricted geographical region within Leicester All attendant undergo an OGTT as the first screening step unless FPG 70 mmoll
Diagnostic procedures
The diagnostic procedure includes a stepwise procedure minimizing the work-load on the general practitioner and includes the questionnaire random capillary blood glucose and HbA1c as screening instruments followed by fasting capillary blood glucose FCBG and an oral glucose tolerance test in everyone with marginally elevated FCBG The diagnostic criteria follow the most recent World Health Organization guidelines 31 and are based on two diagnostic glucose values measured on independent days
Exclusion criteria
Participants are excluded if they already have diabetes are pregnant or lactating or have a severe psychotic illness are house bound or have an illness with a likely survival of less than one year
Outcome measures
Outcome measures from the screening study include measures of the efficacy of the screening campaign the objective health status of patients newly identified by the campaign feasibility as reported by the primary care physician and the economic impact or benefit of the a programme Furthermore a substudy explores the psycho-social and ethical aspects of the screening programme
Methodology - Intervention study
All patients diagnosed as part of the screening programme are invited to enter the ADDITION-study The study will include a minimum of 3000 patients with screen detected diabetes The general practices are randomised to the routine care group standard care as given by the GP or to the intervention group which features a target driven intensive multifactorial approach to treatment The study is an open multicentre parallel group trial with randomisation of general practices Patients are screened and recruited during the period January 1st 2000 and June 30th 2006 The end of follow up is by July 1st 2009 Participation is based on informed consent in accordance with the Declaration of Helsinki
Intensive Treatment strategy
The intensive multifactorial treatment includes lifestyle advices concerning diet physical activity medication adherence and tobacco cessation prescription of aspirin and stepwise increases in pharmacological treatment of blood glucose blood pressure and lipids according to strict targets appendix 1 The treatment targets are as follows
HbA1c 70
Total cholesterol 50 mmoll 45 mmoll if CVD presentbut statin to everyone with total cholesterol 35 mmoll
Blood pressure 13585
Aspirin 75- 150 mgday to everyone on antihypertensive treatment Behavioural advices include
Smoking cessation
Physical activity 30 minday
Healthy diet low fat 600g of fruit and vegetablesday
The treatment targets may be intensified during the study according to the results of other clinical trials published during the study period as the aim is to strive for treatment targets based on the most intensive guidelines available
Within the intensive group a further randomisation allocates 50 of the patients to country specific interventions concerned with improving adherence to lifestyle changes and medication This intervention including the use of motivational interviewing is delivered either by a trained facilitator UK and The Netherlands or through training of practitioners Denmark and is based on a client-centred non-directive counseling style to help patients explore and resolve ambivalence and stimulate lifestyle changes appropriate diabetes self-care and adherence to medical treatment 3233
Pharmacological treatment
The decision on which pharmaceutical drug to use for the individual patients with is made by the clinician as the study is target driven and not a trial comparing different specific drugs The clinician is provided with recommendations for a treatment strategy appendix 1 which should be based on balancing treatment effect side-effects and cost The main priority is achievement of treatment targets with a flexible lifestyle and low rates of side effects such as hypoglycaemia and weight gain
Therapies are adjusted at 2 to 4-weekly intervals until targets are reached thereafter every 3 months HbA1c is taken every third month in between antidiabetic drugs are adjusted according to blood glucose measurements in the interim
Outcome measures see other section
Sample size and statistical power
Based on levels of risk in the conservative-treatment arm of the UKPDS the expected event rate is 3 per year for the combined endpoint all-cause mortality nonfatal myocardial infarction stroke revascularisation or amputation With a sample size of 1350 patients in each arm standard versus intensive treatment the study will allow the detection of a 30 risk reduction in the intervention group at a significance level of 5 with a mean duration of follow-up of 5 years
Timescale
The screening study began in late 2000 and will end by June 30th 2006 Patients are enrolled into the treatment study following diagnosis in the screening study thus the treatment study proceeds along with the evaluation phase of the screening study The follow-up will continue until July 1st 2009
Ethics and safety
The Scientific Ethics Committee in the involved counties in Denmark and the Multipractice Study Committee have accepted the project and the study has been approved by the ethical committees in UK and the Netherlands
A data safety and monitoring committee will have access to all end point data unblinded after 1 3 and 5 years and the study will be terminated if the composite end point including Cardiovascular death non-fatal MI non-fatal stroke revascularisation and amputation should demonstrate a clear advantage of intensive versus standard treatment p0001 or a clear advantage of the standard versus intensive treatment p001
Perspectives of the trial
The results of the study will be of immediate national and international relevance to policy decisions about screening for diabetes and subsequent intensive treatment If the study shows that screening and early intervention markedly reduces the risk of developing premature CVD then the study will have potential important impact at the individual patient level as well as on the societal level If the study fails to show an effect of screening and early intensive treatment then this would have direct impact on future recommendations for screening and treatment regimens and the study could lead to significant savings if it shows that strict treatment targets are not essential in the early phase of the disease The results of the sub-study will inform approaches to health promotion to the management of chronic disease and risk and to strategies to support adherence applicable not only to diabetes but also to other chronic diseases
References and Appendix 1 on wwwadditionaudk
To develop and evaluate strategies for early detection of type 2 diabetes in different countries and different populations
To study whether a multifactorial treatment strategy can reduce CVD-mortality and reduce the incidence of macro- and microvascular complications The treatment strategy consists of motivational interviewing encouraging behavioural changes dietary advises physical activity smoking cessation and intensive pharmacological treatment of blood pressure blood glucose and serum lipids
To identify genetic markers predicting development of diabetic complications
To evaluate health economical consequences of screening and early intervention for type 2 diabetes
Design and methods
The study is an investigator initiated and designed study initiated in Denmark by the two principal investigators planned and conducted in collaboration between the four centers in Denmark UK and the Netherlands The study has two elements a screening study and a subsequent intervention study
In the screening study the feasibility and results of country specific models to identify undiagnosed individuals with Type 2 diabetes will be evaluated
In the treatment study the effects of routine care in general practice according to local and national guidelines will be compared with an intensive ADDITION protocol including structured lifestyle education dietary modification increased physical activity and smoking cessation and intensive treatment of blood glucose blood pressure and lipids and prophylactic aspirin with or without motivational interviewing on mortality macrovascular and microvascular disease Furthermore the impact of treatment on health status treatment satisfaction and health service costs will also be assessed
Methodology - Screening study
In Denmark 300 primary care physicians from 5 different counties Copenhagen Aarhus Ringkøbing Ribe and Sønderjylland participate in the study Diabetes-related information is sent to all individuals aged 40-69 years enrolled in their practice A questionnaire diabetes risk score29 including age gender family history of type 2 diabetes obesity physical activity and previously diagnosed hypertension was used Individuals scoring high on the questionnaire are encouraged to contact their physician for an examination of random blood glucose RGB and HbA1c A step-wise strategy based on RBG HbA1c FPG and OGTT is used to diagnose diabetes In the Netherlands all people aged 50-69 years and listed with the participating primary care physicians is invited to fill in a diabetes risk questionnaire based on the same risk factors as in Denmark Those at high risk of having type 2 diabetes are requested to come for a screening visit at a centre set up near the general practice A stepwise screening strategy based on RBG FPG and OGTT is used to diagnose diabetes In UK different strategies are used in Cambridgeshire and Leicester In Cambridgeshire a search of computerised general practice records is performed using a simple validated risk score based on routine general practice data age gender prescribed medication and body mass index to identify people in the age of 40-69 years at high risk of having undiagnosed diabetes30 Those with a high score undergo a stepwise screening strategy based on RBG FPG and OGTT is used to diagnose diabetes In Leicester all white European subjects aged 40-75 years and Asian black or Chinese subjects aged 25-75 years are invited in a restricted geographical region within Leicester All attendant undergo an OGTT as the first screening step unless FPG 70 mmoll
Diagnostic procedures
The diagnostic procedure includes a stepwise procedure minimizing the work-load on the general practitioner and includes the questionnaire random capillary blood glucose and HbA1c as screening instruments followed by fasting capillary blood glucose FCBG and an oral glucose tolerance test in everyone with marginally elevated FCBG The diagnostic criteria follow the most recent World Health Organization guidelines 31 and are based on two diagnostic glucose values measured on independent days
Exclusion criteria
Participants are excluded if they already have diabetes are pregnant or lactating or have a severe psychotic illness are house bound or have an illness with a likely survival of less than one year
Outcome measures
Outcome measures from the screening study include measures of the efficacy of the screening campaign the objective health status of patients newly identified by the campaign feasibility as reported by the primary care physician and the economic impact or benefit of the a programme Furthermore a substudy explores the psycho-social and ethical aspects of the screening programme
Methodology - Intervention study
All patients diagnosed as part of the screening programme are invited to enter the ADDITION-study The study will include a minimum of 3000 patients with screen detected diabetes The general practices are randomised to the routine care group standard care as given by the GP or to the intervention group which features a target driven intensive multifactorial approach to treatment The study is an open multicentre parallel group trial with randomisation of general practices Patients are screened and recruited during the period January 1st 2000 and June 30th 2006 The end of follow up is by July 1st 2009 Participation is based on informed consent in accordance with the Declaration of Helsinki
Intensive Treatment strategy
The intensive multifactorial treatment includes lifestyle advices concerning diet physical activity medication adherence and tobacco cessation prescription of aspirin and stepwise increases in pharmacological treatment of blood glucose blood pressure and lipids according to strict targets appendix 1 The treatment targets are as follows
HbA1c 70
Total cholesterol 50 mmoll 45 mmoll if CVD presentbut statin to everyone with total cholesterol 35 mmoll
Blood pressure 13585
Aspirin 75- 150 mgday to everyone on antihypertensive treatment Behavioural advices include
Smoking cessation
Physical activity 30 minday
Healthy diet low fat 600g of fruit and vegetablesday
The treatment targets may be intensified during the study according to the results of other clinical trials published during the study period as the aim is to strive for treatment targets based on the most intensive guidelines available
Within the intensive group a further randomisation allocates 50 of the patients to country specific interventions concerned with improving adherence to lifestyle changes and medication This intervention including the use of motivational interviewing is delivered either by a trained facilitator UK and The Netherlands or through training of practitioners Denmark and is based on a client-centred non-directive counseling style to help patients explore and resolve ambivalence and stimulate lifestyle changes appropriate diabetes self-care and adherence to medical treatment 3233
Pharmacological treatment
The decision on which pharmaceutical drug to use for the individual patients with is made by the clinician as the study is target driven and not a trial comparing different specific drugs The clinician is provided with recommendations for a treatment strategy appendix 1 which should be based on balancing treatment effect side-effects and cost The main priority is achievement of treatment targets with a flexible lifestyle and low rates of side effects such as hypoglycaemia and weight gain
Therapies are adjusted at 2 to 4-weekly intervals until targets are reached thereafter every 3 months HbA1c is taken every third month in between antidiabetic drugs are adjusted according to blood glucose measurements in the interim
Outcome measures see other section
Sample size and statistical power
Based on levels of risk in the conservative-treatment arm of the UKPDS the expected event rate is 3 per year for the combined endpoint all-cause mortality nonfatal myocardial infarction stroke revascularisation or amputation With a sample size of 1350 patients in each arm standard versus intensive treatment the study will allow the detection of a 30 risk reduction in the intervention group at a significance level of 5 with a mean duration of follow-up of 5 years
Timescale
The screening study began in late 2000 and will end by June 30th 2006 Patients are enrolled into the treatment study following diagnosis in the screening study thus the treatment study proceeds along with the evaluation phase of the screening study The follow-up will continue until July 1st 2009
Ethics and safety
The Scientific Ethics Committee in the involved counties in Denmark and the Multipractice Study Committee have accepted the project and the study has been approved by the ethical committees in UK and the Netherlands
A data safety and monitoring committee will have access to all end point data unblinded after 1 3 and 5 years and the study will be terminated if the composite end point including Cardiovascular death non-fatal MI non-fatal stroke revascularisation and amputation should demonstrate a clear advantage of intensive versus standard treatment p0001 or a clear advantage of the standard versus intensive treatment p001
Perspectives of the trial
The results of the study will be of immediate national and international relevance to policy decisions about screening for diabetes and subsequent intensive treatment If the study shows that screening and early intervention markedly reduces the risk of developing premature CVD then the study will have potential important impact at the individual patient level as well as on the societal level If the study fails to show an effect of screening and early intensive treatment then this would have direct impact on future recommendations for screening and treatment regimens and the study could lead to significant savings if it shows that strict treatment targets are not essential in the early phase of the disease The results of the sub-study will inform approaches to health promotion to the management of chronic disease and risk and to strategies to support adherence applicable not only to diabetes but also to other chronic diseases
References and Appendix 1 on wwwadditionaudk
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None