STRIVE Study
Research type
Research Study
Full title
Effectiveness and cost of integrating a protocol with use of liraglutide 3.0mg into an obesity service (STRIVE Study)
IRAS ID
232120
Contact name
Melanie Davies
Contact email
Sponsor organisation
University of Leicester
Eudract number
2017-002998-20
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
17/NW/0517, REC
Duration of Study in the UK
3 years, 11 months, 12 days
Research summary
Summary of Research
Adults with obesity are at increased risk of developing associated health complications compared to patients who are of normal weight. Liraglutide 3.0mg (Saxenda) has been recently approved for the treatment of obesity, which has demonstrated its safety and effectiveness. In people with obesity, Liraglutide 3.0mg (Saxenda) has been shown to improve blood pressure and diabetes control and demonstrated that it is a safe and effective treatment option for obesity.However, Liraglutide 3.0mg (Saxenda) is not equally effective in all people with obesity and the high cost of the medication makes it less attractive to the health service for use routinely in obesity clinics. Previous studies have shown that approximately 14% of the people who will use the medication will be able to achieve more than 15% weight loss at one year after the treatment (“good” responders) and the vast majority of the “good” responders will achieve significant weight loss from the first months of treatment.
The aim of this study is to investigate the effectiveness and cost-effectiveness of a targeted prescribing pathway that would provide a pragmatic means by which to optimise the use of Liraglutide 3.0mg (Saxenda) in a specialist obesity service. This approach is expected to minimise the side-effects and unnecessary exposure of those who will not achieve significant weight loss with Liraglutide 3.0mg (Saxenda), optimise the costs of the medications and target the patients who will benefit more from its use.
Summary of Results
The STRIVE study aimed to compare the proportion of participants with severe and complicated obesity achieving weight loss of at least 15% at 52 weeks with 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 provided in Tier 3 services alone.
The study was a 26 month, parallel, two group, open-label, real-world, Randomised Controlled Trial design for people with severe and complex obesity (defined as BMI ≥35 kg/m2 with at least one major obesity-related comorbidity) who were referred to a Tier 3 obesity service. The first 52 weeks of the study (after randomisation) determined whether using the targeted prescribing pathway in a Tier 3 setting resulted in more participants attaining ≥15% weight loss compared with standard care. The second 52 weeks of the study assessed whether participants who lose ≥15% of their baseline weight by the first 52 weeks were more likely to maintain ≥15% weight loss for another 52 weeks in the targeted prescribing pathway compared with standard care.
Participants were randomised 2:1 to receive either 1) a targeted prescribing pathway (intervention), or 2) standard care (control). Participants in the control group followed the best medical care provided by the Tier 3 service at the relevant site. Participants in the intervention group received the same standard care as those in the control group. Additionally, at baseline, LIRA 3mg was prescribed to all intervention participants at a starting dose of 0.6mg daily. Dose escalation of LIRA occurred according to a pre-specified titration protocol, from 0.6mg to a maximum of 3.0mg daily. Continued use of LIRA 3mg was based upon the participants response to the treatment in terms of them achieving pre-defined weight loss targets at 16, 32, and 52 weeks.
The primary endpoint was a binary outcome indicating whether weight loss of ≥15% was achieved at 52 weeks. Secondary endpoints included anthropometric measures, quality of life measures, co-morbidity outcomes, medication use, and safety endpoints.
It was initially planned that 384 participants would be recruited. This target was revised to 392 following a protocol amendment on advice of the Data Safety Monitoring Committee and Trial Steering Committee. This recruitment target was met, with 392 participants randomised (132 control; 260 intervention). Of these, 93 control and 201 intervention participants were eligible for the complete case population for the primary analysis at 52 weeks.
Of the 260 intervention group participants, 182 (70.0%) passed the first stopping rule to continue on LIRA 3mg treatment at 16 weeks, 113 (43.5%) passed the second stopping rule at 32 weeks, and 54 (20.8%) passed the third stopping rule at 52 weeks.
The primary analyses showed that 6.5% of the control group achieved ≥15% weight loss at 52 weeks compared with 25.4% of the intervention group. Therefore, the intervention group were over five times as likely to achieve ≥15% weight loss than the control group (OR = 5.19; 95% CI= 2.09, 12.88; p < 0.001). The primary analyses were conducted in the complete cases population. Similar results were shown for the primary outcome in the ITT and per protocol populations.
Furthermore, the intervention arm was statistically superior to the control arm for weight loss of ≥5% and ≥10% at 16, 32, and 52 weeks. The intervention group was also significantly more likely to have ≥5% weight loss at 104 weeks than the control group (OR = 2.44; 95% CI = 1.23, 4.84; p = 0.010). The difference between the two groups at 104 weeks for ≥10% and ≥15% weight loss did not reach statistical significance. However, at 104 weeks, the intervention group lost on average 5.44 kg (95% CI = 2.53, 8.34 kg; p < 0.001) more than the control group.
Analyses of other anthropometric outcomes showed that there were also statistically significant improvements in BMI and waist circumference at 52 and 104 weeks in the intervention group compared with the control group. This finding held in both the complete cases and responder analyses.
Statistical comparisons were not made for the other secondary outcomes. However, many of the outcomes were indicative of a greater improvement in the intervention than control group. For example, for the King’s College Obesity Staging System, there was a lower percentage of intervention than control participants in the advanced disease group at weeks 52 and 104, despite a slightly higher percentage of intervention participants having advanced disease at baseline. There was a similar pattern for the severe depression category of the PHQ-9 (depression test questionnaire) at 52 weeks (but not at 104 weeks), the possible Obstructive Sleep Apnoea category of the Epworth sleepiness scale at 52 and 104 weeks, and the likely Obstructive Sleep Apnoea category of the Stop Bang questionnaire at 52 and 104 weeks.
There was not a clear improvement in glycaemic status in the intervention group, however this was affected to some extent by the definition of glycaemia as those still on LIRA 3mg could not be categorised as having diabetes remission. Conversely, there was a marked difference in the percentage of participants achieving a HbA1c target of ≤7% at 52 (control: 35.3%; intervention: 81.5%) and 104 weeks (control: 41.2%; intervention 74.4%). There were similar results for a HbA1c target of ≤6.5%. The mean change from baseline in HbA1c at 52 and 104 weeks was minimal for the control group and approximately 6.6 mmol/mol (-0.6 %) and -6.0 mmol/mol (-0.6 %), respectively, in the intervention group.
Hypertension did not show a clear pattern between the two treatment arms over the 52 and 104 weeks. Blood pressure also appeared to reduce to a greater extent in the control arm than the intervention arm. There were also minimal differences between the two groups in terms of cholesterol and lipid measures. This suggests that the targeted treatment pathway may have had limited benefits in terms of blood pressure, cholesterol, and lipids.
Referrals to bariatric surgery were slightly higher in the intervention (9.6%) than control (3.8%) group, with a similar proportion having surgery by 104 weeks (2.3% vs 3.0%, respectively).
At both week 52 and 104, there was a greater improvement in the intervention than control group for all of the EQ5D (quality of life questionnaire) subscales. Indeed, for all subscales except anxiety/depression, the score improved from baseline in the intervention group, but worsened from baseline in the control group. The EQ5D (quality of life questionnaire) visual analogue scale also improved in the intervention group at 52 weeks, but not at 104 weeks. The PHQ-9 (depression test questionnaire) scores also suggested that the intervention group improved to a greater extent than the control group at weeks 52 and 104. The IWQOL-Lite (quality of life questionnaire) scores showed the opposite pattern with the control group improving more at week 52, and declining to a lesser extent at week 104.
The Epworth Sleepiness Scale and Stop Bang questionnaire showed minimal differences in change from baseline between the two treatment groups. Treatment satisfaction was greater in the intervention than control group for all subscales at 52 and 104 weeks, however results should be interpreted with caution because a very small number of control participants completed the treatment satisfaction questionnaire.
The total MET-minutes/week increased from baseline to week 52 in both groups to a similar extent. However, the change from a baseline to week 104 was a decrease in the control group and a substantial increase in the intervention group.
There were more safety events in the intervention group than the control group. In particular, 42.3% of intervention group participants had experienced gastrointestinal symptoms by 52 weeks compared with 3.0% of control group participants. However, symptoms were generally mild (only six episodes were classed as an Serious Adverse Event out of 561 Adverse Events), no new safety signals for LIRA 3mg were identified, and the hypoglycaemia rate was very low in both groups, regardless of which definition was used, with no severe hypoglycaemic episodes reported. Finally, safety and tolerability were consistent with the Glucagon like Peptide-1 receptor agonist class in general.
Together, these results strongly indicate that using LIRA 3mg as part of a targeted prescribing pathway with standard Tier 3 care results in greater, and sustained, weight loss. The results were also indicative of improvements in quality of life, glycaemic measures, and physical activity. There were no apparent improvements in blood pressure, cholesterol, or lipids. Care should be given in ensuring that potential users are aware of the potential side effects.REC name
North West - Liverpool Central Research Ethics Committee
REC reference
17/NW/0517
Date of REC Opinion
29 Sep 2017
REC opinion
Further Information Favourable Opinion