The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture.
OBJECTIVE
To evaluate the effects of MK-0677, an orally active growth hormone (GH) secretagogue, on functional recovery from hip fracture in previously mobile older individuals.


METHODS
Placebo-controlled, randomized, double-blind trial.


METHODS
Thirteen medical centers in England, Sweden, Denmark, Belgium, Switzerland, Canada, and the United States. Patients were recruited between 3 and 14 days postoperatively, or no more than 18 days postfracture, at acute care hospitals and rehabilitation centers.


METHODS
One hundred sixty-one hip-fracture patients were enrolled. Entry criteria included consenting hip-fracture patients who were aged 65 and older and who were ambulatory before their fracture, medically stable postoperatively, and mentally competent. Patients were excluded if they had multiple fractures or severe trauma, diabetes mellitus, cancer, uncontrolled hypertension, congestive heart failure, or total hip replacement in the involved extremity.


METHODS
Random assignment to 6 months of daily treatment with MK-0677 or placebo. Patients were followed for an additional 6 months after completion of therapy.


METHODS
Change from Week 6 to Week 26 in a panel of functional performance measures. Additional outcome measures included change in the Sickness Impact Profile for Nursing Homes (SIP-NH), the ability to live independently, and insulin-like growth factor I (IGF-I) levels.


RESULTS
MK-0677 treatment increased serum IGF-I levels by 84% (95% confidence interval (CI)=63-107), compared with an increase of 17% (95% CI=8-28) on placebo. There were no significant differences between MK-0677 and placebo in improvement in functional performance measures or in the overall SIP-NH score. Although MK-0677 patients showed greater improvement relative to placebo in three of four lower extremity functional performance measures, in the physical domain of the SIP, and in the ability to live independently, these differences were not statistically significant.


CONCLUSIONS
Although MK-0677 treatment increased serum IGF-I, it is uncertain whether clinically significant effects on physical function were achieved. Measuring function in clinical trials in hip-fracture patients is difficult because of the lack of validated outcome measures, high variability, and the lack of a baseline assessment. Present functional performance measures may not be sufficiently responsive for use as the primary endpoint of small intervention studies; alternatively, stimulation of GH may not result in significant functional improvement.
Bach
Mark A
MA
Merck Research Laboratories, Rahway, New Jersey, USA.
Rockwood
Kenneth
K
Zetterberg
Carl
C
Thamsborg
Gorm
G
Hébert
Réjean
R
Devogelaer
Jean-Pierre
JP
Christiansen
Jens Sandahl
JS
Rizzoli
René
R
Ochsner
J Lockwood
JL
Beisaw
Norman
N
Gluck
Oscar
O
Yu
Leisure
L
Schwab
Thomas
T
Farrington
Jeanne
J
Taylor
Alice M
AM
Ng
Jennifer
J
Fuh
Vivian
V
D000203:Activities of Daily Living; D000284:Administration, Oral; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D015577:Geriatric Assessment; D005947:Glucose / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006620:Hip Fractures / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology / Q000534:rehabilitation; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D016743:Mental Competency; D020127:Recovery of Function; D012449:Safety; D018434:Sickness Impact Profile; D013141:Spiro Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D005947:Glucose; D006442:Glycated Hemoglobin; D007211:Indoles; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D013141:Spiro Compounds; C094817:ibutamoren mesylate