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High vs. Standard Dose Rifampicin for Effusive Tuberculous Pericarditis

ConditionsTuberculous PericarditisHIV Status
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Cape Town

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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)

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

Disqualifiers

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

Rifampin-resistant TB

Severe concurrent opportunistic infection

Contraindication to placement of intra-pericardial catheter

Trial design

Design model

Parallel

Treatments tested in this trial

  • high dose Rifampicin (RIF)

    Drug

    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 used

Treatment groups

60 Participants
are divided into 2 treatment groups
Group A: Arm 1: Standard of care (RIF10)No intervention 0 interventions
Group B: Arm 2: High-dose RIF (RIF35)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Drug exposure in PCF and mediates in Mtb load

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

Time frame
72 hours and 52 weeks

Secondary outcomes

1

Mortality between study arms

To investigate clinical outcome by mortality (attributable to PCTB and all cause)

Time frame
week 8 and 52 weeks
2

re-accumulation of pericardial effusion between study arms

To investigate clinical outcome by comparing clinical evidence of constrictive pericarditis between study arms

Time frame
52 weeks
3

TB-IRIS between study arms

To investigate clinical outcome by comparison of the incidence of TB immune reconstitution inflammatory syndrome (TB-IRIS) between study arms

Time frame
52 weeks
4

Constrictive pericarditis between the study arms

Comparison of the incidence of constrictive pericarditis between the study arms

Time frame
52 weeks

Other outcomes

1

To investigate the safety and tolerability of RIF35 for PCTB by:

1. The occurrence of Grade 3 or 4 transaminitis during ATT 2. Permanent discontinuation of the RIF10 or RIF35 ATT arm at week 8

Time frame
week 8 and 52 weeks
2

Discontinuation rate

Comparison of discontinuation rates between study arms Comparison of discontinuation rates between study arms

Time frame
52 weeks
3

Change in Mtb bacterial load

To investigate early change in Mtb bacterial load by measures other than culture TTP (CFU, Xpert ct values, ddPCR, CEQ, Mtb RNA, FujiLAM) in PCF over 72 hours by treatment allocation

Time frame
72 hours
4

Relationships between pericardial Mtb-specific T cells with Mtb bacterial load

To determine relationships between pericardial Mtb-specific T cells with Mtb bacterial load, treatment response and outcome in PCTB

Time frame
52 weeks

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Cape Town

Lead sponsor

Source ClinicalTrials.gov
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