High-dose versus standard-dose rifampicin for tuberculous pericardial effusion

IMPI-3 - A Randomized Controlled Trial of High vs. Standard Dose Rifampicin for Effusive Tuberculous Pericarditis

This trial will try whether a higher oral dose of rifampicin clears tuberculous pericardial infection faster than the standard dose in adults with pericardial effusion, including people with or without HIV.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Cape Town (Academic / other)
• Locations: 2 sites (Mthatha, Eastern Cape and 1 other locations)
• Trial ID: NCT04521803 on ClinicalTrials.gov

What this trial studies

This is a Phase 2b randomized, placebo-controlled, double-blinded trial conducted at two South African centers that will enroll 100 adults with effusive tuberculous pericarditis. Participants are stratified by HIV status and pericardial fluid Xpert Ultra result and randomized 1:1 to receive either standard anti-tuberculosis therapy plus placebo or standard therapy plus high-dose rifampicin (35 mg/kg) for two months, followed by a six-month total treatment course with standard continuation therapy. Pericardiocentesis is performed as clinically indicated and microbiologic confirmation from pericardial fluid or probable-case criteria are used for enrollment. Safety and pericardial drug exposure and mycobacterial clearance will be compared between the two groups.

Who should consider this trial

Good fit: Adults aged 18 or older with confirmed or probable tuberculous pericardial effusion who can undergo pericardiocentesis and start first-line anti-tuberculosis therapy within five days are eligible, regardless of HIV status.

Not a fit: People with rifampin-resistant TB, severe renal failure requiring dialysis, or contraindications to pericardiocentesis are unlikely to benefit from this trial intervention.

Why it matters

Potential benefit: If successful, higher-dose rifampicin could increase drug levels in the pericardial space, speed bacterial clearance, and reduce complications or relapses of tuberculous pericarditis.

How similar studies have performed: Higher rifampicin doses have improved drug exposure and shown some efficacy signals in pulmonary TB, but using high-dose rifampicin specifically for pericardial TB is largely novel and not yet proven.

Eligibility criteria

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

Where this trial is running

Mthatha, Eastern Cape and 1 other locations

• Nelson Mandela Academic Hospital — Mthatha, Eastern Cape, South Africa (Not_yet_recruiting)
• Groote Schuur Hospital — Cape Town, Western Cape, South Africa (Recruiting)

Study contacts

• Principal investigator: Mpiko U Ntsekhe, Professor — Department of Cardiology, Groote Schuur Hospital
• Study coordinator: Mpumi U Maxebengula, BCom

Conditions Tuberculous Pericarditis; HIV Status