High vs. Standard Dose Rifampicin for Effusive Tuberculous Pericarditis
High vs. Standard Dose Rifampicin for Effusive Tuberculous Pericarditis
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.
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.
Inclusion Criteria:

 1. Aged >18 years

 2. Suspected PCTB with confirmed pericardial effusion on echocardiography (i.e., echo
 free space of ≥1 cm anterior to the right ventricle in diastole)

 3. Consent to study participation including testing for HIV-1 (if HIV status is unknown)

 4. 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:

 1. Evidence of pericarditis with microbiologic confirmation of Mtb- infection
 elsewhere in the body and/or

 2. Exudative, lymphocyte predominant effusion with elevated adenosine deaminase (≥35
 U/L)

 5. Participant will undergo pericardiocentesis (as per clinical indication)

 6. Within 5 days of ATT initiation

 Exclusion Criteria:

 1. Glomerular filtration rate <30ml/min or renal failure requiring dialysis

 2. Rifampin-resistant TB

 3. Severe concurrent opportunistic infection

 4. Contraindication to placement of intra-pericardial catheter

 5. Failed pericardiocentesis procedure and/or failure of placement of intra-pericardial
 catheter

 6. 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.

 7. In females: a positive urine pregnancy test result

 8. Confirmed autoimmune disorders (e.g. systemic lupus erythematosus)

 Additional Exclusions for Gadolinium contrasted CMR

 1. Any implanted devices that are not MR compatible (e.g. pacemaker, defibrillators,
 cerebral aneurysm clips, cochlear implants etc.)

 2. Claustrophobia

 3. Gadolinium allergy

 4. Inability to lie on a flat surface for prolonged periods of time (e.g. severe
 congestive cardiac failure)

 5. Breastfeeding