Study register · detailRCT (open-label, multicenter) · Cachexia · 1997
The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative.
Timpone et al.·AIDS Research and Human Retroviruses
MixedGRADEModerate135 citations
Samplen = 52 Pat.
Duration12 weeks
ControlFour active treatment arms
EndpointWeight change
Blindingoffen
DesignRCT (open-label, multicenter)
Cannabinoidthc
Max. dose5.0 mg
Routeoral
”Key finding
Megestrol acetate 750 mg (±dronabinol) produced significant weight gain, while dronabinol alone showed weight loss.
Summary
n=52 HIV wasting patients, dronabinol 2.5 mg 2×/d vs. megestrol 750 mg/d vs. combinations, 12 weeks; mean weight change dronabinol monotherapy: -2.0 ± 1.3 kg vs. megestrol 750 mg: +6.5 ± 1.1 kg (p<0.0001); dronabinol alone inferior in weight gain.
P
PopulationAdults with HIV wasting syndrome (mean CD4+ count 59 cells/µl), n=52 randomised, 47 with ≥1 follow-up visit
ControlFour active treatment arms (no placebo arm); comparison among each other
O
OutcomeWeight change over 12 weeks: D −2,0 kg, M750 +6,5 kg, M750+D +6,0 kg, M250+D −0,3 kg (p=0,0001); no significant differences in adverse events or CD4+ changes
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
Downgraded for
Imprecision
Quality profile
Sample size★★★★★
BlindingOpen-label
Effect sizeMixed
Citations / year★★★★★
Authors
Timpone JG, Wright DJ, Li N, Egorin MJ, Enama ME, Mayers J, Galetto G.
This randomized, open-labeled, multicenter study was designed to assess safety and pharmacokinetics of dronabinol (Marinol) tablets and megestrol acetate (Megace) micronized tablets, alone and in combination, for treatment of HIV wasting syndrome. Weight and quality of life data were also collected. Fifty-two patients (mean CD4+ count, 59 cells/microliter) were randomized to one of four treatment arms: dronabinol 2.5 mg twice/day (D); megestrol acetate 750 mg/day (M750); megestrol acetate 750 mg/day+dronabinol 2.5 mg twice/day (M750+D); or megestrol acetate 250 mg/day+dronabinol 2.5 mg twice/day (M250+D). After therapy initiation, 47 patients returned for at least one visit, and 39 completed the planned 12 weeks of study visits. Occurrence of adverse events, drug discontinuation, new AIDS-defining conditions, or CD4+ T lymphocyte changes were not statistically significantly different among arms. Serious adverse events assessed as related to dronabinol included CNS events (e.g., confusion, anxiety, emotional lability, euphoria, hallucinations) and those assessed as related to megestrol acetate included dyspnea, liver enzyme changes, and hyperglycemia. The mean weight change +/- SE over 12 weeks was as follows: D, -2.0 +/- 1.3 kg; M750, +6.5 +/- 1.1 kg; M750+D, +6.0 +/- 1.0 kg; and M250+D, -0.3 +/- 1.0 kg (difference among treatment arms, p = 0.0001). Pharmacokinetic parameters measured after 2 weeks of therapy for M750 were Cmax = 985 ng/ml and AUC = 22,487 ng x hr/ml, and for dronabinol and its active metabolite (HO-THC), respectively, were Cmax = 2.01; 4.61 ng/ml and AUC = 5.3; 23.7 ng x hr/ml. For megestrol acetate, but not dronabinol, there was a positive correlation at week 2 between both Cmax and AUC with each of the following: (1) weight change, (2) breakfast visual analog scale for hunger (VASH) score, and (3) dinner VASH score.