Browsing by Author "Lombard, Carl"

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    An all-oral 6-month regimen for multidrug resistant Tuberculosis: A multicenter randomized controlled clinical trial (the Next Study)
    Esmail, Aliasgar ; Oelofse, Suzette ; Lombard, Carl ; Perumal, Rubeshan ; Variava, Ebrahim ; Martinson, Neil
    Rationale: Improving treatment outcomes while reducing drug toxicity and shortening the treatment duration to 6 months remains an aspirational goal for the treatment of multi drug resistant /rifampicin-resistant tuberculosis(MDR/RR-TB). Objectives: To conduct a multicenter randomized controlled trial in adults with MDR/RR-TB(i.e., without resistance to fluoroquinolones or aminoglycosides) . Methods: Participants were randomly assigned(1:1ratio)to a 6 month all-oral regimen that included levofloxacin, bed aquiline, and linezolid or the standard-of-care(SOC)>9-month World Health Organization(WHO)-approved injectable-based regimen. The primary endpoint was a favorable WHO-defined treatment outcome (which mandates that prespecified drugs substitution is counted as an unfavorable outcome)24 months after treatment initiation. The trial was stopped prematurely when bed aquiline-based therapy became the standard of care in South Africa. Measurements and Main Results: In total,93 of 111 randomized participants(44 in the comparator arm and 49 in the intervention alarm) were included in the modified intention-to-treatanalysis;51(55%)were HIV coinfected(medianCD4count,158cells/ml).Participants in the intervention arm were 2.2 times more likely to experience a favorable 24-month outcome than participants in the SOC arm(51%[25of49]vs. 22.7%[10of44];riskratio,2.2[1.2–4.1];P=0.006).Toxicity-related drug substitution occurred more frequently in the SOC arm(65.9%[29of44] vs.34.7%[17of49];P=0.001)],82.8%(24of29)owing to kanamycin (mainly hearing loss; replaced by bed aquiline) in the SOC arm, and 64.7% (11of17) owing to fluoroquinolones or aminoglycosides (mainly anemia) in the intervention alarm. Adverse event–related treatment discontinuation in the safety population was more common in the SOC arm(56.4%[31of55]vs.32.1%[17of 56];P=0.007).However, grade 3 adverse events were more common in the intervention alarm(55.4%[31of56]vs.32.7[18of55];P=0.022). Culture conversion was significantly better in the intervention arm (hazardratio,2.6[1.4–4.9];P=0.003)after censoring those with bed aquiline replacement in the SOC arm(and this pattern remained consistent after censoring for drug replacement in both arms ;P=0.01). Conclusions: Compared with traditional injectable-containing regimens, an all-oral 6-month levofloxacin, bed aquiline, and linezolid–containing MDR/RR-TB regimen was associated with a significantly improved 24-month WHO-defined treatment outcome (predominantly owing to toxicity-related drugs substitution).However, drug toxicity occurred frequently in both arms. These findings form strategies to develop future regimens for MDR/RR-TB. Clinical trial registered with www.clinicaltrials.gov (NCT02454205).
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    Integrated health system intervention aimed at reducing type 2 diabetes risk in women after gestational diabetes in South Africa (IINDIAGO): a randomised controlled trial protocol
    (BMJ Publishing Group, 2024) Norris, Shane A.; Zarowsky, Christina; Murphy, Katherine; Ware, Lisa Jayne; Lombard, Carl; Matjila, Mushi; Chivese, Tawanda; Muhwava, Lorrein Shamiso; Mutabazi, Jean Claude; Harbron, Janetta; Fairall, Lara R.; Lambert, Estelle; Levitt, Naomi
    Introduction South Africa has a high prevalence of gestational diabetes mellitus (GDM; 15%) and many of these women (48%) progress to type 2 diabetes mellitus (T2DM) within 5 years post partum. A significant proportion (47%) of the women are not aware of their diabetes status after the index pregnancy, which may be in part to low postnatal diabetes screening rates. Therefore, we aim to evaluate a intervention that reduces the subsequent risk of developing T2DM among women with recent GDM. Our objectives are fourfold: (1) compare the completion of the nationally recommended 6-week postpartum oral glucose tolerance test (OGTT) between intervention and control groups; (2) compare the diabetes risk reduction between control and intervention groups at 12 months’ post partum; (3) assess the process of implementation; and (4) assess the cost-effectiveness of the proposed intervention package. Methods and analyses Convergent parallel mixed methods study with the main component being a pragmatic, 2-arm individually randomised controlled trial, which will be carried out at five major referral centres and up to 26 well-baby clinics in the Western Cape and Gauteng provinces of South Africa. Participants (n=370) with GDM (with no prior history of either type 1 or type 2 diabetes) will be recruited into the study at 24–36 weeks’ gestational age, at which stage first data collection will take place. Subsequent data collection will take place at 6–8 weeks after delivery and again at 12 months. The primary outcome for the trial is twofold: first, the completion of the recommended 2-hour OGTT at the well-baby clinics 6–8 weeks post partum, and second, a composite diabetes risk reduction indicator at 12 months. Process evaluation will assess fidelity, acceptability, and dose of the intervention. Ethics and dissemination Ethics approval has been granted from University of Cape Town (829/2016), University of the Witwatersrand, Johannesburg (M170228), University of Stellenbosch (N17/04/032) and the University of Montreal (2019-794). The results of the trial will be disseminated through publication in peerreviewed journals and presentations to key South African Government stakeholders and health service providers. Protocol version 1 December 2022 (version #2). Any protocol amendments will be communicated to investigators, Human Ethics Research Committees, trial participants, and trial registries. Trial registration number PAN African Clinical Trials Registry (https://pactr.samrc.ac.za) on 11 June 2018 (identifier PACTR201805003336174).