A Phase 2 Randomized Trial of Pre-emptive NPH Insulin Versus Usual Reactive Diabetes Management for Preventing Hyperglycaemia After Intra-articular Triamcinolone Acetonide Injection in Adults With Type 2 Diabetes and Knee Osteoarthritis
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 125
- 试验地点
- 1
- 主要终点
- Percentage of Continuous Glucose Monitoring Time Above 180 mg/dL During the First 72 Hours After Corticosteroid Injection
研究概览
简要总结
Steroid injections used to treat painful joints can temporarily increase glucose levels in people with type 2 diabetes. This study will test whether a short course of pre-emptive neutral protamine Hagedorn, NPH, insulin can reduce high glucose after a standard corticosteroid injection into the knee.
Adults with type 2 diabetes who are scheduled to receive one intra-articular injection of triamcinolone acetonide 40 mg for knee osteoarthritis will be randomly assigned to one of two groups. The experimental group will receive a prespecified NPH insulin regimen beginning immediately after the injection and continuing for three doses. The comparison group will continue usual reactive diabetes management without pre-emptive NPH insulin.
Both groups will use blinded continuous glucose monitoring and scheduled capillary glucose testing. The main outcome is the percentage of continuous glucose monitoring time above 180 mg/dL during the first 72 hours after the corticosteroid injection. Hypoglycaemia, rescue treatment, healthcare contacts, treatment burden, acceptability and adverse events will also be assessed.
详细描述
Intra-articular corticosteroid injections can produce clinically important but transient hyperglycaemia in people with type 2 diabetes. Published studies have largely characterised this glucose response rather than testing a standardised strategy to prevent it.
PREVENT-SIH is a phase 2, randomised, parallel-group trial in adults with type 2 diabetes managed without insulin or insulin secretagogues. All participants will receive a clinically indicated, standardised intra-articular injection of triamcinolone acetonide crystalline suspension 40 mg into one index knee for symptomatic knee osteoarthritis.
Participants will be randomly assigned 1:1 to a pre-emptive NPH insulin pathway or usual reactive diabetes management. The pre-emptive pathway comprises three weight-based NPH doses starting immediately after the corticosteroid injection, with prespecified glucose-based dose modification, withholding and discontinuation rules. Both groups will continue stable background diabetes medication and will receive identical blinded continuous glucose monitoring, capillary glucose monitoring, safety instructions, scheduled contacts and rescue thresholds.
Continuous glucose monitoring data will be collected for a 72-hour baseline period and for at least 96 hours after injection. The primary analysis will compare the percentage of valid readings above 180 mg/dL during the first 72 hours after injection, adjusted for baseline continuous glucose monitoring time above 180 mg/dL, site and HbA1c stratum. Rescue treatment and other post-randomisation diabetes treatment changes will be retained in the primary treatment-policy analysis.
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
- Single (Outcomes Assessor)
盲法说明
Participants and clinicians administering or adjusting insulin will know the assigned intervention. Continuous glucose monitoring displays will be blinded to participants and treating clinicians. The statistician or outcomes assessor who derives the prespecified continuous glucose monitoring outcomes from coded data will remain masked to treatment assignment until the primary analysis dataset and derivation programs have been finalised.
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 40 to 80 years at consent.
- •Documented diagnosis of type 2 diabetes for at least 6 months.
- •HbA1c from 6.5% through 9.0% measured within 30 days before randomisation.
- •Symptomatic osteoarthritis of one knee for which the treating clinician has independently determined that an intra-articular corticosteroid injection is clinically indicated.
- •Planned administration of one intra-articular injection of triamcinolone acetonide crystalline suspension 40 mg into the index knee.
- •Diabetes managed without insulin, sulfonylureas or meglitinides.
- •Permitted glucose-lowering medications at stable doses for at least 30 days before randomisation.
- •Estimated glomerular filtration rate at least 45 mL/min/1.73 m² within 60 days before randomisation.
- •Capillary glucose from 90 through 250 mg/dL immediately before the injection.
- •Ability and willingness to perform scheduled capillary glucose testing, administer or receive subcutaneous insulin if assigned, follow hypoglycaemia instructions and remain contactable through day
- •Ability to wear the study continuous glucose monitoring device and provide informed consent.
排除标准
- •Type 1 diabetes, latent autoimmune diabetes in adults, pancreatogenic diabetes or another specific diabetes type requiring insulin.
- •Current basal, prandial, premixed or pump insulin treatment.
- •Current sulfonylurea or meglitinide treatment.
- •HbA1c below 6.5% or above 9.0%.
- •Capillary glucose below 90 mg/dL or above 250 mg/dL immediately before injection.
- •Fasting glucose above 250 mg/dL, random glucose above 300 mg/dL, clinically significant ketonaemia or hyperglycaemia requiring immediate treatment during screening.
- •Estimated glomerular filtration rate below 45 mL/min/1.73 m².
- •Severe hepatic impairment or another condition expected to materially alter insulin clearance or hypoglycaemia risk.
- •Level 3 hypoglycaemia requiring third-party assistance during the previous 6 months.
- •Documented impaired awareness of hypoglycaemia.
- •Pregnancy, planned pregnancy during study participation or breastfeeding.
- •Oral, intravenous or intramuscular corticosteroid use within 30 days before the study injection.
- •Any intra-articular, epidural, periarticular or soft-tissue corticosteroid injection within 30 days before the study injection.
- •Planned additional systemic or injected corticosteroid exposure before the day-7 assessment.
- •Acute febrile illness, active systemic infection or acute deterioration in health at screening or injection.
- •Suspected septic arthritis, infection over the injection site, prosthetic index knee, uncontrolled bleeding disorder or another contraindication to knee injection.
- •Known allergy or clinically significant hypersensitivity to triamcinolone acetonide, human NPH insulin, insulin aspart, protamine, lidocaine or required excipients.
- •Known allergy to continuous glucose monitoring adhesive or a skin condition preventing sensor use.
- •Cognitive, visual, physical or social limitation that would prevent safe glucose testing, insulin administration, hypoglycaemia treatment or study contact.
- •Participation in another interventional study likely to affect glucose or corticosteroid response.
- •Any condition that, in the investigator's documented judgement, makes participation unsafe for a reason not otherwise captured above.
研究组 & 干预措施
Usual Reactive Diabetes Management
Participants will continue stable background diabetes medication without pre-emptive NPH insulin. They will receive blinded continuous glucose monitoring, the same scheduled capillary glucose testing, safety instructions, study contacts and common rescue pathway as the experimental group. Additional non-emergency medication changes may be made by the treating diabetes clinician when clinically necessary and will be documented.
干预措施: Triamcinolone Acetonide Knee Injection (Drug)
Pre-emptive NPH Insulin Pathway
Participants will receive three subcutaneous doses of human NPH insulin beginning within 30 minutes after intra-articular triamcinolone acetonide injection and repeated approximately 24 and 48 hours later. The initial dose is 0.10 units/kg, maximum 16 units. Subsequent doses are modified according to prespecified capillary-glucose and hypoglycaemia criteria. Participants will continue stable background diabetes medication and receive blinded continuous glucose monitoring, scheduled capillary glucose testing, safety contacts and the common rescue pathway.
干预措施: Insulin Isophane Human, NPH, Pre-emptive Algorithm (Drug)
结局指标
主要结局
Percentage of Continuous Glucose Monitoring Time Above 180 mg/dL During the First 72 Hours After Corticosteroid Injection
时间窗: From completion of the intra-articular corticosteroid injection through 72 hours after injection
The numerator is the number of valid continuous glucose monitoring readings above 180 mg/dL from the recorded completion time of the intra-articular injection through exactly 72 hours. The denominator is the total number of valid readings during that window. The result is expressed as a percentage. A directly observed outcome requires at least 80% of expected readings and no uninterrupted data gap longer than 6 hours. Participants not meeting this requirement have a missing primary outcome for statistical handling; missing readings are not counted as being within or above range.
次要结局
- Percentage of Continuous Glucose Monitoring Time Above 250 mg/dL(From completion of the injection through 72 hours after injection)
- Continuous Glucose Monitoring Area Under the Curve Above 180 mg/dL(From completion of the injection through 72 hours after injection)
- Mean Sensor Glucose(From completion of the injection through 72 hours after injection)
- Peak Sensor Glucose(From completion of the injection through 72 hours after injection)
- Time to Peak Sensor Glucose(From completion of the injection through 72 hours after injection)
- Percentage of Continuous Glucose Monitoring Time in Range, 70 to 180 mg/dL(From completion of the injection through 72 hours after injection)
- Percentage of Continuous Glucose Monitoring Time Below 70 mg/dL(From completion of the injection through 72 hours after injection)
- Percentage of Continuous Glucose Monitoring Time Below 54 mg/dL(From completion of the injection through 72 hours after injection)
- Participants With Clinically Significant Hypoglycaemia(From completion of the injection through day 7)
- Participants Requiring Rescue Glucose-Lowering Treatment(From completion of the injection through 72 hours after injection)
- Number of Unscheduled Diabetes-Related Clinical Contacts or Healthcare Encounters(From completion of the injection through day 7)
- Participant-Reported Treatment Burden Score(Day 4)
研究者
Saima Abass Tahammal
Medical Director Endocrinology
Shifa International Hospital