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Delamanid effective in multidrug resistant TB

Patients with multidrug-resistant tuberculosis may now have another treatment option with delamanid, data from a multinational study suggest.

Researchers worldwide tested delamanid (Otsuka), a nitro-dihydro-imidazooxazole derivative in patients with pulmonary MDR-TB. The randomized, placebo-controlled trial included 481 patients who received 100 mg delamanid twice daily, 200 mg twice daily or placebo for 2 months. The patients also received the drug regimen recommended by WHO guidelines. Sputum cultures were analyzed weekly.

Among patients who received 100 mg delamanid twice daily with their background regimen, 45.4% demonstrated sputum conversion in liquid broth by 2 months. In contrast, among patients who received placebo with their background regimen, 29.6% had a sputum culture conversion in liquid broth. Among those who received 200 mg delamanid with their background regimen, 41.9% had a sputum culture conversion. All of these findings were similar in sputum culture conversions in solid medium.

Figure 1. Lea Pehme, MD, and nurse Evi Kivi are examining a chest X-ray for signs of pulmonary tuberculosis at the Tartu University Clinics in Tartu, Estonia.

Figure 2. A patient in the TB ward at the Hospital Nacional Sergio E. Bernales in Lima, Peru.

Images: Venturi R; Otsuka

Adverse events were similar across all of the treatment arms, and were mild to moderate in severity. There were fewer adverse events among patients receiving 100 mg delamanid twice daily compared with those receiving the 200 mg twice-daily dose. Although no episodes of prolonged QT interval were associated any clinical events, the frequency of prolonged QT interval was higher in the delamanid groups compared with the placebo group.

“A second large, randomized, controlled trial of 6 months of treatment with delamanid as part of a full background drug regimen and including patients who have coinfection with HIV and are receiving ART has been initiated and is designed to provide data on 30 months of follow-up patients,” the researchers wrote. “It is important to learn more about the use of delamanid in combination with other new and existing antimycobacterial agents to develop better regimens for multi-drug resistant tuberculosis.”

References:

Gler MT. N Engl J Med. 2012;366:2151-2160.

Disclosures:

The researchers report no relevant financial disclosures.

Patients with multidrug-resistant tuberculosis may now have another treatment option with delamanid, data from a multinational study suggest.

Researchers worldwide tested delamanid (Otsuka), a nitro-dihydro-imidazooxazole derivative in patients with pulmonary MDR-TB. The randomized, placebo-controlled trial included 481 patients who received 100 mg delamanid twice daily, 200 mg twice daily or placebo for 2 months. The patients also received the drug regimen recommended by WHO guidelines. Sputum cultures were analyzed weekly.

Among patients who received 100 mg delamanid twice daily with their background regimen, 45.4% demonstrated sputum conversion in liquid broth by 2 months. In contrast, among patients who received placebo with their background regimen, 29.6% had a sputum culture conversion in liquid broth. Among those who received 200 mg delamanid with their background regimen, 41.9% had a sputum culture conversion. All of these findings were similar in sputum culture conversions in solid medium.

Figure 1. Lea Pehme, MD, and nurse Evi Kivi are examining a chest X-ray for signs of pulmonary tuberculosis at the Tartu University Clinics in Tartu, Estonia.

Figure 2. A patient in the TB ward at the Hospital Nacional Sergio E. Bernales in Lima, Peru.

Images: Venturi R; Otsuka

Adverse events were similar across all of the treatment arms, and were mild to moderate in severity. There were fewer adverse events among patients receiving 100 mg delamanid twice daily compared with those receiving the 200 mg twice-daily dose. Although no episodes of prolonged QT interval were associated any clinical events, the frequency of prolonged QT interval was higher in the delamanid groups compared with the placebo group.

“A second large, randomized, controlled trial of 6 months of treatment with delamanid as part of a full background drug regimen and including patients who have coinfection with HIV and are receiving ART has been initiated and is designed to provide data on 30 months of follow-up patients,” the researchers wrote. “It is important to learn more about the use of delamanid in combination with other new and existing antimycobacterial agents to develop better regimens for multi-drug resistant tuberculosis.”

References:

Gler MT. N Engl J Med. 2012;366:2151-2160.

Disclosures:

The researchers report no relevant financial disclosures.

    Perspective
    Joel Ernst

    Joel Ernst

    This is an important trial, as it represents a major step forward for a drug with a novel mechanism of action against Mycobacterium tuberculosis. The inclusion of delamanid in a regimen for multidrug-resistant TB increased the frequency of culture-negative sputum after 2 months of therapy, indicating that it can contribute to new regimens for drug-resistant TB. In addition, while this trial was not designed to test the value of delamanid in shortening the course of treatment for drug-susceptible TB, it will be logical to proceed with trials to examine the value of delamanid in drug-susceptible TB. Together with another new drug with a novel mechanism of action (bedaquiline, formerly TMC-207), new options for treatment of MDR-TB are emerging as the problem of MDR-TB continues to worsen. In addition, since the mechanisms of action of delamanid and bedaquiline are distinct from one another and from those of established anti-TB drugs, it is now possible to consider the development of new drug regimens for TB that combine delamanid and bedaquiline

    • Joel Ernst, MD
    • Infectious Disease News editorial board

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