IMPI-3 - A Randomized Controlled Trial of High vs. Standard Dose Rifampicin for Effusive Tuberculous Pericarditis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 4
- 主要终点
- Drug exposure in PCF and mediates in Mtb load
研究概览
简要总结
The investigators hypothesise that high dose RIF (RIF35) will increase pericardial fluid RIF exposure and so enhance mycobacterial clearance, compared to standard of care dosing (RIF10).
This Phase 2b randomized, placebo-controlled, double-blinded trial will evaluate the efficacy and safety of RIF 35mg/kg compared 10mg/kg, added to standard first-line ATT, for the treatment of PCTB.
详细描述
IMPI-3 - A Randomized Controlled Trial of High vs. Standard Dose Rifampicin for Effusive Tuberculous Pericarditis
Phase 2b Randomized, placebo-controlled, double-blinded clinical trial
The trial will enroll 100 adult participants with pericardial TB from two research sites in South Africa, with no exclusions being made on the basis of sex/gender, racial or ethnic group.
Consenting participants will be stratified by HIV status and PCF GX-Ultra status, then randomized 1:1 to receive either standard of care anti-tuberculosis treatment (ATT) or standard of care plus high dose Rifampicin (RIF), both administered orally for 2 months, followed by a continuation phase of 4 months' RH at standard doses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Neither participants nor the investigators will be aware of the participant's treatment allocation until the end of the study (double blinding). Blinding will be maintained by manufacture of placebo tablets similar in appearance and packaging to that of the study drug, with centralized dispensing by the study pharmacist. Unmasking procedures are detailed by SOP.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged >18 years
- •Suspected PCTB with confirmed pericardial effusion on echocardiography (i.e., echo free space of ≥1 cm anterior to the right ventricle in diastole)
- •Consent to study participation including testing for HIV-1 (if HIV status is unknown)
- •Microbiologically detected Mtb in PCF or diagnosis of probable PCTB. Probable PCTB (in the absence of a positive pericardial fluid culture) will be defined as per Mayosi et al.4:
- •Evidence of pericarditis with microbiologic confirmation of Mtb- infection elsewhere in the body and/or
- •Exudative, lymphocyte predominant effusion with elevated adenosine deaminase (≥35 U/L)
- •Participant will undergo pericardiocentesis (as per clinical indication)
- •Within 5 days of ATT initiation
排除标准
- •Glomerular filtration rate <30ml/min or renal failure requiring dialysis
- •Rifampin-resistant TB
- •Severe concurrent opportunistic infection
- •Contraindication to placement of intra-pericardial catheter
- •Failed pericardiocentesis procedure and/or failure of placement of intra-pericardial catheter
- •Any disease or condition in which the use of the standard anti-TB drugs (or any of their components) are contraindicated. This includes, but is not limited to, allergy to any TB drug or their components.
- •In females: a positive urine pregnancy test result
- •Confirmed autoimmune disorders (e.g. systemic lupus erythematosus)
- •Additional Exclusions for Gadolinium contrasted CMR
- •Any implanted devices that are not MR compatible (e.g. pacemaker, defibrillators, cerebral aneurysm clips, cochlear implants etc.)
- •Claustrophobia
- •Gadolinium allergy
- •Inability to lie on a flat surface for prolonged periods of time (e.g. severe congestive cardiac failure)
- •Breastfeeding
研究组 & 干预措施
Arm 2: High-dose RIF (RIF35)
Simulations were performed to determine the dose of RIF required to achieve the most equitable drug exposures across the weight range, 30 to 100 kg. Demographic data of a reference cohort of TB patients (n = 1225), with or without HIV-1 coinfection, recruited in clinical trials conducted in West Africa and South Africa were used for the simulations35-38. An additional 12 250 virtual patients were generated using the weight and height distributions of the 1225 patients to increase the number of patients with a weight close to the boundaries of the weight range. Parameter estimates of the population PK model for RIF were used to simulate (100 replicates) RIF exposures22. Four dosing scenarios were evaluated using the weight-band based dosing with 4-drug FDC tablets and extra RIF tablets with each tablet containing 150 mg or 600 mg RIF. The FDC tablets were assumed to have 20% reduced bioavailability based on data from a clinical trial where the same formulation was used39
干预措施: high dose Rifampicin (RIF) (Drug)
Arm 1: Standard of care (RIF10)
Dosing of the daily oral RHZE fixed dose combination (FDC) will be according to WHO weight bands
结局指标
主要结局
Drug exposure in PCF and mediates in Mtb load
时间窗: 72 hours and 52 weeks
To determine whether higher dose rifampicin (35mg/kg) increases pericardial fluid (AUC) RIF levels and increases time to positivity of mycobacterial culture at 72 hours compared to standard dose Rifampicin
次要结局
- Mortality between study arms(week 8 and 52 weeks)
- re-accumulation of pericardial effusion between study arms(52 weeks)
- TB-IRIS between study arms(52 weeks)
- Constrictive pericarditis between the study arms(52 weeks)
- CMR evidence(52 weeks)
研究者
Mpiko Ntsekhe
National Principal Investigator
University of Cape Town