High vs. Standard Dose Rifampicin for Effusive Tuberculous Pericarditis
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: high dose Rifampicin (RIF).
- Who it may be relevant to
- Registry conditions: Tuberculous Pericarditis, HIV Status. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- South Africa
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
IMPI-3 - A Randomized Controlled Trial of High vs. Standard Dose Rifampicin for Effusive Tuberculous Pericarditis
Overview
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.
Detailed description
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.
Interventions
- Drug high dose Rifampicin (RIF)
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 p
Primary outcome measures
- Drug exposure in PCF and mediates in Mtb load [Time frame: 72 hours and 52 weeks]
Secondary outcome measures (5)
- Mortality between study arms [Time frame: week 8 and 52 weeks]
- re-accumulation of pericardial effusion between study arms [Time frame: 52 weeks]
- TB-IRIS between study arms [Time frame: 52 weeks]
- Constrictive pericarditis between the study arms [Time frame: 52 weeks]
- CMR evidence [Time frame: 52 weeks]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Triple blind
- Primary purpose
- Basic science
Study locations
South Africa · 2 centers
- Nelson Mandela Academic Hospital — Mthatha
- Groote Schuur Hospital — Cape Town
Identifiers
NCT: NCT04521803 · IMPI-3 DMID 20-0007