EFFECTIVENESS AND COST OF INTEGRATING A PROTOCOL WITH USE OF LIRAGLUTIDE 3.0 MG INTO AN OBESITY SERVICE: (STRIVE Study)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 392
- 试验地点
- 5
- 主要终点
- Weight Loss of ≥15% From Baseline (Complete Cases)
研究概览
简要总结
A two year, parallel, two group, open-label, real-world randomised controlled trial (RCT) design for subjects with severe and complex obesity who are referred to a Tier 3 or equivalent specialist weight management/obesity service. Participants will be randomised to receive 1) standard care (obesity-specialist care), or 2) targeted prescribing pathway (obesity-specialist care plus targeted use of Liraglutide 3.0mg [LIRA 3mg] with pre-specified stopping rules for the medication). The aim of the study is to compare the effectiveness, budget impact, and cost-effectiveness between the two groups in a real-world setting among otherwise largely unselected patients.
详细描述
Summary of Trial Design A two year, parallel, two group, open-label, real-world, RCT design for patients with severe and complex obesity who are referred to a Tier 3 obesity service (including patients who are referred to a Tier 3 service as part of the bariatric surgery pathway). The total duration of participation will be 104 weeks (+/-2 weeks).
The first 52 weeks of the study (after randomisation) will determine whether using the targeted prescribing pathway in a Tier 3 setting will result in more participants attaining ≥15% weight loss compared with standard care. The second 52 weeks of the study will assess whether patients who lose ≥15% of their baseline weight by the first 52 weeks are more likely to maintain ≥15% weight loss for another 52 weeks in the targeted prescribing pathway compared with standard care. Further, budget impact, cost-effectiveness, improvement in obesity-related co-morbidities, complementary aspects of safety, effectiveness, adherence, and treatment satisfaction of both treatment groups will be assessed and compared.
Participants will be randomised in a 2:1 fashion to either the intervention (targeted prescribing pathway + standard care) or control (standard care) group (2 intervention: 1 control). The control group will receive standard care in a specialist obesity service (Tier 3 or equivalent), according to the best practice in each site and can include total or partial meal replacement strategies. The intervention group will receive the same standard care as the control group (i.e. according to the best practice in each site) plus all participants will initially receive LIRA with pre-specified stopping rules. The targeted prescribing pathway: participants who do not meet the definition of a 'early and good responder' (defined as achieving ≥5% weight loss at 16 weeks, ≥10% weight loss at 32 weeks and ≥15% weight loss at 52 weeks) will have their LIRA 3mg treatment stopped. It is important to note that all participants will be analysed in the group to which they are randomised; in particular, participants in the intervention group who stop receiving LIRA 3mg will remain in the intervention group and will continue to receive standard care for the remainder of the study as per the targeted prescribing pathway (albeit, the part of the pathway where LIRA 3mg is not prescribed; see Figure 1).
The study is intentionally designed to reflect a pragmatic "real-world" scenario and each Tier 3 provider may require a different number of visits for their programme. However, study appointments for data collection, titration reviews, application of the stopping rules of LIRA 3mg, and dispensing will be standardised for all of the five sites.
Intervention (Targeted Prescribing Pathway)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •be aged between 18-75 years old (inclusive)
- •understand written and spoken English
- •be able to give in informed consent
- •a body mass index ≥35 kg/m2,
- •have been referred to Tier 3 weight management or equivalent service in one of the five participating sites,
- •have a stable body weight (less than 5kg self-reported change during the previous 12 weeks),
- •Participant must be able to meet at least one of the inclusion criteria listed below:
- •prediabetes (defined as established diagnosis of impaired fasting glycaemia (IFG) from GP and/or established diagnosis of impaired glucose tolerance (IGT) from GP and/or HbA1C 42-47 mmol/mol (6-6.4%) without glucose lowering medications, at a blood test during the last 6 months) and/or
- •type 2 diabetes [defined as established diagnosis of Type II diabetes from GP and/or HbA1C ≥48 mmol/mol (>6.5%) at a blood test during the last 6 months] being treated with any combination of lifestyle, metformin, sulphonylureas, thiazolidinediones (TZDs) or SGLT-2, and/or
- •hypertension treated (defined as being on antihypertensive treatment with or without a diagnosis of hypertension from GP) or untreated (defined as Systolic Blood Pressure (SBP) ≥140 mmHg at two consecutive visits at the Tier 3 clinic), and/or
- •obstructive sleep apnoea (on CPAP or established diagnosis of Apnoea Hypopnoea Index ≥15 at sleep studies during the last 12 months)
排除标准
- •Diagnosis of Type 1 diabetes
- •Type 2 diabetes with treatment on DPP-IV or insulin currently
- •Treatment with GLP-1 receptor agonists within the last 6 months and/or have a history of GLP-1 receptor agonist intolerance.
- •Treatment with anti-obesity drugs within the last 12 weeks prior to randomisation
- •eGFR ≤30ml/min/1.73m2 on serum testing over the last 26 weeks
- •Females referred to the clinic because of fertility problem
- •Females of child bearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using or willing to use adequate contraceptive methods during the study period
- •Have terminal illness
- •Are not primarily responsible for their own care
- •Not willing or able to give informed consent
- •Any other significant disease or disorder which in the opinion of the investigator, may either put the participants at risk or may influence the result of the study or the participant's ability to participate
- •Untreated or uncontrolled hypothyroidism/hyperthyroidism defined as thyroid- stimulating hormone >6 mIU/liter or <0.4 mIU/liter
- •Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC)
- •Personal history of non-familial medullary thyroid carcinoma
- •History of chronic pancreatitis or idiopathic acute pancreatitis
- •Amylase levels three times higher than the upper normal range
- •Obesity induced by other endocrinologic disorders (e.g. Cushing's Syndrome)
- •Current or history of treatment with medications that may cause significant weight gain, within 12 weeks prior to screening, including systemic corticosteroids (except for a short course of treatment, i.e. 7-10 days), atypical antipsychotic and mood stabilizers (e.g. clozapine, olanzapine, valproic acid and its derivatives, and lithium)
- •History of major depressive episode during the last 2 years
- •History of initiation of antidepressants during the last 12 weeks
- •Simultaneous participation in other clinical trials of investigational drugs, lifestyle or physical activity interventions.
- •Previous surgical treatment for obesity (excluding liposuction if performed >1 year before trial entry)
- •History of other severe psychiatric disorders
- •History of known or suspected abuse of alcohol and/or narcotics
- •History of major depressive episode during the last 2 years
- •Simultaneous participation in other clinical trials of investigational drugs, lifestyle or physical activity interventions. Patients will only be able to take part following participation in a previous clinical trial after a wash-out period of 16 weeks.
研究组 & 干预措施
Targeted Prescribing Pathway (LIRA 3mg + Standard Care)
Standard care plus targeted use of the intervention Liraglutide (LIRA) 3mg when pre-specified stopping rules for the medication apply
干预措施: Saxenda (Drug)
Targeted Prescribing Pathway (LIRA 3mg + Standard Care)
Standard care plus targeted use of the intervention Liraglutide (LIRA) 3mg when pre-specified stopping rules for the medication apply
干预措施: Specialist Obesity Management Services (Other)
Standard Care
standard Tier 3 obesity specialist service care
干预措施: Specialist Obesity Management Services (Other)
结局指标
主要结局
Weight Loss of ≥15% From Baseline (Complete Cases)
时间窗: 52 weeks
Proportion of participants with severe and complicated obesity achieving weight loss of ≥15% at 52 weeks with the use of a targeted prescribing pathway (i.e. use of LIRA 3mg according to a pre-specified protocol in combination with standard care provided in Tier 3 services) versus standard care alone in a Tier 3 service.
Weight Loss of ≥15% From Baseline (Intention to Treat)
时间窗: 52 weeks
Proportion of participants with severe and complicated obesity achieving weight loss of ≥15% at 52 weeks with the use of a targeted prescribing pathway (i.e. use of LIRA 3mg according to a pre-specified protocol in combination with standard care provided in Tier 3 services) versus standard care alone in a Tier 3 service.
Weight Loss of ≥15% From Baseline (Per Protocol Without Excluded Concomitant Medications)
时间窗: 52 weeks
Proportion of participants with severe and complicated obesity achieving weight loss of ≥15% at 52 weeks with the use of a targeted prescribing pathway (i.e. use of LIRA 3mg according to a pre-specified protocol in combination with standard care provided in Tier 3 services) versus standard care alone in a Tier 3 service.
Weight Loss of ≥15% From Baseline (Per Protocol)
时间窗: 52 weeks
Proportion of participants with severe and complicated obesity achieving weight loss of ≥15% at 52 weeks with the use of a targeted prescribing pathway (i.e. use of LIRA 3mg according to a pre-specified protocol in combination with standard care provided in Tier 3 services) versus standard care alone in a Tier 3 service.
次要结局
- Participant Compliance With Treatment (Intention to Treat)(104 weeks)
- Cessation of Treatment Due to Adverse Effects (Intention to Treat)(104 weeks)
- Participant Attendance at Appointments (Intention to Treat)(104 weeks)
- Patient Stopping of Treatment (Intention to Treat)(52 weeks)
- Completion of Tier 3 Despite Liraglutide Cessation by 16 Weeks (Intention to Treat)(52 weeks)
- Completion of Tier 3 Despite Liraglutide Cessation by 32 Weeks (Intention to Treat)(52 weeks)
- Started on Anti-obesity Drugs at 52 Weeks (Intention to Treat)(52 weeks)
- Started on Anti-obesity Drugs at 104 Weeks (Intention to Treat)(104 weeks)
- Referral to Other Obesity Interventions (Intention to Treat)(104 weeks)
- Referral to Other Obesity Interventions by Site (Intention to Treat)(104 weeks)
- Bariatric Surgery Completion (Intention to Treat)(104 weeks)
- Absolute Waist Circumference Change (Complete Cases)(104 weeks)
- Kings College Obesity Staging (KCOS) Score (Complete Cases)(104 weeks)
- Weight Loss of ≥5% From Baseline (Complete Cases)(104 weeks)
- Weight Loss of ≥10% From Baseline (Complete Cases)(104 weeks)
- Weight Loss of ≥15% From Baseline (Complete Cases)(104 weeks)
- Maintenance of ≥15% Weight Loss Until 104 Weeks (Complete Cases)(104 weeks)
- Absolute Weight Change (Complete Cases)(104 weeks)
- Percentage Weight Change (Complete Cases)(104 weeks)
- Absolute BMI Change (Complete Cases)(104 weeks)
- Patient Health Questionnaire-9 (Complete Cases)(104 weeks)
- Epworth Sleepiness Scale (Complete Cases)(104 weeks)
- Stop Bang Questionnaire (Complete Cases)(104 weeks)
- Glycaemic Status (Complete Cases)(104 weeks)
- HbA1c ≤7% for Those With Diabetes at Baseline (Complete Cases)(104 weeks)
- HbA1c ≤6.5% for Those With Diabetes at Baseline (Complete Cases)(104 weeks)
- Hypertension (Complete Cases)(104 weeks)
- Weight Loss of ≥5% From Baseline (Responder Population)(104 weeks)
- Weight Loss of ≥10% From Baseline (Responder Population)(104 weeks)
- Weight Loss of ≥15% From Baseline (Responder Population)(104 weeks)
- Maintenance of ≥15% Weight Loss Until 104 Weeks (Responder Population)(104 weeks)
- Percentage Weight Change (Responder Population)(104 weeks)
- Absolute BMI Change (Responder Population)(104 weeks)
- Absolute Waist Circumference Change (Responder Population)(104 weeks)