Tuberculous PericarditisPhase 2IMPI-3NCT04521803
High vs. Standard Dose Rifampicin for Effusive Tuberculous Pericarditis
A Phase 2 study testing high dose Rifampicin (RIF) in people with Tuberculous Pericarditis and HIV Status, run by University of Cape Town at 2 sites in South Africa.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculous Pericarditis, HIV Status
- What is being tested?
- high dose Rifampicin (RIF)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 2 sitesSouth Africa
- Study dates
- 10 Jan 2022to 10 Jun 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 14Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
South Africa2 sites
Groote Schuur Hospital
Cape Town, Western Cape, 7925
Nelson Mandela Academic Hospital
Mthatha, Eastern Cape, 5099
About this study
Official title: IMPI-3 - A Randomized Controlled Trial of 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.
Read the 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.
- Conditions
- Tuberculous Pericarditis, HIV Status
- Being tested
- high dose Rifampicin (RIF)
- Medical subject headings
- Pericarditis, Tuberculous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Standard of care (RIF10) | No intervention | Dosing of the daily oral RHZE fixed dose combination (FDC) will be according to WHO weight bands |
| Arm 2: High-dose RIF (RIF35) | Experimental | 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 used39 Receives: Drug: high dose Rifampicin (RIF) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 72 hours and 52 weeks
Secondary outcomes (5)
Mortality between study arms
To investigate clinical outcome by mortality (attributable to PCTB and all cause)
Measured: week 8 and 52 weeks
re-accumulation of pericardial effusion between study arms
To investigate clinical outcome by comparing clinical evidence of constrictive pericarditis between study arms
Measured: 52 weeks
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
Measured: 52 weeks
Constrictive pericarditis between the study arms
Comparison of the incidence of constrictive pericarditis between the study arms
Measured: 52 weeks
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
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2020
- Study start10 Jan 2022
- Primary completion26 Mar 2026
- Study completion10 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculous PericarditisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participant identification numbers (PID), assigned at the screening visit, will be used throughout the study. After signing the informed consent document; eligible participants will be stratified by HIV status and then further stratified by GX-Ultra status to ensure equal allocation regardless of HIV status and likely subsequent culture status. An electronic randomization tool will be used to randomize the subgroups in a 1:1 ratio. The randomization list will be generated and updated by the study coordinator, trial pharmacist, or statistician who will have no direct contact with trial participants or involvement with the assessment for eligibility in the trial.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cape Town
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mpiko Ntsekhe, University of Cape Town
- Investigators
- Mpiko U Ntsekhe, Professor, Principal investigator, Department of Cardiology, Groote Schuur Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04521803
- Sponsor's protocol ID
- IMPI-3 DMID 20-0007
- Acronym
- IMPI-3
- Status last verified
- Mar 2025
- First submitted
- 16 Jul 2020
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IMPI-3 - A Randomized Controlled Trial of High vs. Standard Dose Rifampicin for Effusive Tuberculous Pericarditis
- ClinicalTrials.gov ID
- NCT04521803
- Acronym / sponsor ID
- IMPI-3 / IMPI-3 DMID 20-0007
- Conditions
- Tuberculous Pericarditis, HIV Status
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- University of Cape TownUniversity, hospital or other
- Study start
- 10 Jan 2022 (actual)
- Primary completion
- 26 Mar 2026 (actual)
- Study completion
- 10 Jun 2026 (actual)
- First posted
- 21 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Participant identification numbers (PID), assigned at the screening visit, will be used throughout the study. After signing the informed consent document; eligible participants will be stratified by HIV status and then further stratified by GX-Ultra status to ensure equal allocation regardless of HIV status and likely subsequent culture status. An electronic randomization tool will be used to randomize the subgroups in a 1:1 ratio. The randomization list will be generated and updated by the study coordinator, trial pharmacist, or statistician who will have no direct contact with trial participants or involvement with the assessment for eligibility in the trial.
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Standard of care (RIF10) | No intervention | –Dosing of the daily oral RHZE fixed dose combination (FDC) will be according to WHO weight bands |
| Arm 2: High-dose RIF (RIF35) | Experimental | 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 used39 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- Participant will undergo pericardiocentesis (as per clinical indication)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Drug | Arm 2: High-dose RIF (RIF35) |
Primary outcome
Drug exposure in PCF and mediates in Mtb load
Time frame: 72 hours and 52 weeks
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
5 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2026.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mpiko U Ntsekhe, Professor principal investigator
Department of Cardiology, Groote Schuur Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing high dose Rifampicin (RIF) in people with Tuberculous Pericarditis and HIV Status, run by University of Cape Town at 2 sites in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Drug exposure in PCF and mediates in Mtb load (time frame: 72 hours and 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026; AzTrials last refreshed its copy on 6 Nov 2026.