Tesamorelin · research summary

Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial.

The lancet. HIV · 2019. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

12-month randomized, double-blind, placebo-controlled trial
“The study was randomized and double-blind, with identical placebo as a comparator.”

Subjects

Men and women with HIV infection and hepatic fat fraction ≥5%
“61 men and women with HIV-infection and hepatic fat fraction (HFF) ≥5% by proton magnetic resonance spectroscopy were randomized to receive tesamorelin 2mg daily vs. identical placebo for 12 months at two academic centers.”

Sample size

61 participants randomized (26 tesamorelin, 28 placebo in primary analysis)
“The sample size for the primary endpoint analysis was 26 in the tesamorelin group and 28 in the placebo group, as shown in Figure 1.”

Duration

12 months
“The study consisted of a 12-month, double-blind treatment phase during which participants were randomized in a 1:1 ratio to receive tesamorelin 2mg daily or identical placebo.”

Reported findings

Tesamorelin reduced hepatic fat fraction compared to placebo
“Tesamorelin (N=26) reduced HFF compared to placebo (N=28), with an absolute effect size of −4.1% (95% CI −7.6, −0.7, P=0.02), corresponding to a −37% (CI −67, −7, P=0.02) relative reduction from baseline.”
Tesamorelin prevented the progression of fibrosis compared to placebo
“Among the entire cohort, tesamorelin prevented the progression of fibrosis during the treatment period, with 2 individuals (10.5%) showing progression in the tesamorelin group versus 9 (37.5%) in the placebo group (P=0.04) (Figure 3).”
Tesamorelin reduced C-reactive protein levels compared to placebo
“Tesamorelin reduced CRP (effect size −4.7 mg/L [95% CI −9.2, −0.2], P=0.04, Table 2) compared to placebo but did not have any effect on adiponectin.”

Limitations stated by the authors

Study not designed as a therapeutic trial for NASH; could not definitively assess effects on FDA-recommended NASH endpoints
“In contrast, the study was not designed as a therapeutic trial for NASH, not all patients had significant steatohepatitis, and there was a range of baseline NAS scores. Therefore, we could not definitively assess effects on endpoints recommended by the FDA as appropriate for late-stage studies of NASH therapeutics, namely improvements in histological evidence of fibrosis, or inflammation, or both.”

Source: PubMed 31611038 · DOI 10.1016/S2352-3018(19)30338-8 · all study summaries

Reported findings

Tesamorelin reduced hepatic fat fraction compared to placebo

“Tesamorelin (N=26) reduced HFF compared to placebo (N=28), with an absolute effect size of −4.1% (95% CI −7.6, −0.7, P=0.02), corresponding to a −37% (CI −67, −7, P=0.02) relative reduction from baseline.”

Tesamorelin prevented the progression of fibrosis compared to placebo

“Among the entire cohort, tesamorelin prevented the progression of fibrosis during the treatment period, with 2 individuals (10.5%) showing progression in the tesamorelin group versus 9 (37.5%) in the placebo group (P=0.04) (Figure 3).”

Tesamorelin reduced C-reactive protein levels compared to placebo

“Tesamorelin reduced CRP (effect size −4.7 mg/L [95% CI −9.2, −0.2], P=0.04, Table 2) compared to placebo but did not have any effect on adiponectin.”

Limitations stated by the authors

Study not designed as a therapeutic trial for NASH; could not definitively assess effects on FDA-recommended NASH endpoints

“In contrast, the study was not designed as a therapeutic trial for NASH, not all patients had significant steatohepatitis, and there was a range of baseline NAS scores. Therefore, we could not definitively assess effects on endpoints recommended by the FDA as appropriate for late-stage studies of NASH therapeutics, namely improvements in histological evidence of fibrosis, or inflammation, or both.”