PandrTB:

Pharmacometrics to Advance Novel Regimens for Drug-Resistant Tuberculosis 

Challenge

The toxicity of drugs used for the treatment of multidrug-resistant TB (MDR-TB) remains a major barrier in effective treatment. 

Compounded by the fact that 10-15%1 of patients acquire further drug resistance over the course of treatment,  MDR-TB patients pay a heavy price to successfully overcome the disease, including experiencing impaired vision, hearing loss, or other substantial side effects. 

The endTB and endTB-Q clinical trials utilize novel regimens of TB drugs to provide MDR-TB patients with shorter treatment. 

With gaps in pharmacometrics – there is limited information on MDR-TB drug doses that would maximize efficacy while minimizing toxicity. 

There is also a crucial need to analyze the interaction of drugs with novel regimens and drugs used to treat comorbidities like HIV, and now, COVID-19.

Approach

In Pakistan, endTB and endTB-Q clinical trials are being implemented by IRD in collaboration with the Indus Hospital and Health Network (IHHN). With a resource-effective sub-study integrated into existing trial process flows, PandrTB has been initiated in Karachi at IHHN since February 2021.

PandrTB aims to analyse the PK-PD of TB drugs. This is analysis of the drugs inside a patient’s body: from intake, to absorption and distribution, as well as the effects on TB and the patient’s body. Blood samples of participants enrolled in the experimental arms of the endTB and endTB-Q clinical trials are to be collected at 5 different points.

Over the course of a patient’s 6-month or 9-month long treatment and subsequent follow-ups, sputum samples will be collected to test and track responses to treatment. In aligning patients’ visits to the hospital for endTB / endTB-Q with the visits required for PandrTB, patients are not inconvenienced or exposed to any increased risk of COVID-19 transmission.

PandrTB is sponsored by the University of Cape Town and funded by the Wellcome Trust. It is currently recruiting patients in Peru, Lesotho, South Africa, and now also Pakistan.

Impact

Worldwide, PandrTB aims to enroll ~650 participants. In Pakistan, since initiation (on 23rd February 2021) till the end of April 2021, 25 people were approached for the study out of which 17 gave consent to participate. 10 out of the 17 study participants have already given blood samples, on at least 1 visit out of 5. 

This study is an important step in increasing access to information on more less toxic treatment regimens, and bringing patients closer to effective treatment. In defining optimal drug doses, future MDR-TB patients may have the opportunity to overcome their disease without worrying about developing further drug resistance or experiencing life-altering side effects.

The study is currently on-going until 2022.