Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04521803
Other study ID # IMPI-3 DMID 20-0007
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date January 10, 2022
Est. completion date February 28, 2026

Study information

Verified date February 2024
Source University of Cape Town
Contact Mpumi U Maxebengula, BCom
Phone 0727633386
Email mpumi.maxebengula@uct.ac.za
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 80
Est. completion date February 28, 2026
Est. primary completion date September 15, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

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 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

Locations

Country Name City State
South Africa Groote Schuur Hospital Cape Town Western Cape
South Africa Nelson Mandela Academic Hospital Mthatha Eastern Cape

Sponsors (1)

Lead Sponsor Collaborator
University of Cape Town

Country where clinical trial is conducted

South Africa, 

Outcome

Type Measure Description Time frame Safety issue
Other To investigate the safety and tolerability of RIF35 for PCTB by: The occurrence of Grade 3 or 4 transaminitis during ATT
Permanent discontinuation of the RIF10 or RIF35 ATT arm at week 8
week 8 and 52 weeks
Other Discontinuation rate Comparison of discontinuation rates between study arms Comparison of discontinuation rates between study arms 52 weeks
Other 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 72 hours
Other 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 52 weeks
Other Mtb-induced markers of host cell death pathways and Mtb bacterial load in PCTB To assess whether there is association between Mtb-induced markers of host cell death pathways and Mtb bacterial load in PCTB 52 weeks
Primary 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 72 hours and 52 weeks
Secondary Mortality between study arms To investigate clinical outcome by mortality (attributable to PCTB and all cause) week 8 and 52 weeks
Secondary re-accumulation of pericardial effusion between study arms To investigate clinical outcome by comparing clinical evidence of constrictive pericarditis between study arms 52 weeks
Secondary 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 52 weeks
Secondary Constrictive pericarditis between the study arms Comparison of the incidence of constrictive pericarditis between the study arms 52 weeks
Secondary CMR evidence To investigate clinical outcome by evidence on week 52 CMR of:
Constrictive physiology
Pericardial inflammation
Pericardial thickening
Pericardial fibrosis
Inflammatory exudative or hemorrhagic pericardial effusion
52 weeks
See also
  Status Clinical Trial Phase
Completed NCT00810849 - A Trial of Adjunctive Prednisolone and Mycobacterium w Immunotherapy in Tuberculous Pericarditis Phase 3