A total of 287 potential participants were screened consecutively for the study between June 2005 and December 2007. Of these people, 110 met the entry criteria and consented to enrol (55 in each arm); of these 70 (64%) were female. The median age was 32. Baseline characteristics were evenly matched across both arms of the study, apart from the duration between TB treatment and ART, which was longer in the prednisone arm.
Six patients defaulted for more than seven days or were lost to follow up (all in the placebo arm, p = 0.01). Three chose to quit the study drug in the placebo arm versus one in the prednisone arm. There were three deaths in the prednisone arm and two in the placebo arm (p = 0.7). After enrolment, ten patients were diagnosed with rifampicin resistance (four vs six in prednisone and placebo arms, p = 0.5).
In an intent-to-treat analysis, there was a significant reduction of the need for medical interventions in patients in the prednisone arm, compared to the placebo arm, with a cumulative primary endpoint of one (interquartile range 0 to 3) median number of hospital days in the prednisone arm vs three (IQR 0 to 9) in the placebo arm (p = 0.046). Cumulatively, there were 282 vs 463 days of hospitalization and 27 vs 31 procedures in the prednisone and placebo arms, respectively.
During the 12 weeks of follow up, 35 patients (20 on placebo and 15 on prednisone) were switched to open-label prednisone (p=0.03). However, 18 out of 20 in the placebo arm switched within the first four weeks because they were deteriorating on the study drug (in their case placebo). By contrast, in the prednisone arm, only five patients switched to open-label prednisone in the first four weeks - most switched afterwards because they had initially improved on the study drug and then had relapsed after completing the four weeks on treatment.
There were also reductions, or significant differences, in a number of secondary outcomes. For instance, a five-point score (which looked at, and graded, changes in different symptoms in each patient) demonstrated significant symptom improvement in prednisone vs placebo arm at week two (p = 0.001) and week four (p=0.03). “More patients in the prednisone arm have significantly better symptom response at weeks two and four; while patients in the placebo arm had symptom deterioration,” said Dr Meintjes.
Likewise, chest X-rays of those with pulmonary infiltrates improved significantly more rapidly; and quality-of-life and performance scores were significantly better at weeks two and four in those on prednisone. CRP measurements improved from a median 104 mg/L at baseline to 34 mg/L by week one in those in the prednisone arm, while CRP improved more slowly in the placebo arm (mostly after the four weeks of study drug).
“On the flipside, the important thing was that there was no excess of adverse events or infections or serious infections in the prednisone arm,” said Dr Meintjes. There was no difference in mortality. During the course of follow up, about 30 patients in both arms had symptoms that might be attributed to corticosteroid side effects (such as hypertension, oedema, hypoglycaemia, hypomonia, acne, gastritis, Cushingold features). But during the first four weeks on study, only eight patients had side-effects in the prednisone arm vs three in the placebo, which did not reach statistical significance (p = 0.11). There were similar numbers of infections in both arms, but severe infections occurred in only two people in the prednisone arm vs four in the placebo arm (p = 0.4). There were no episodes of KS.