Somatostatin-based therapies for external gastrointestinal fistulas: Updated meta-analysis of randomized clinical trials

Table 1 Baseline characteristics of included randomized controlled trials, n (%)

Ref.	Follow-up, days	Type of study	Intervention group	Control group	No. of patients	Age years1	Male	Fistula type	High output	Low output	Output mL/day
Torres et al[1], 1992	20.4	Prospective, randomized, multicenter. Blinding status is unclear	TPN combined with continuous intravenous infusion of somatostatin (250 µg/hour)	TPN alone for first 15 days; supportive care included nasogastric suction, antibiotics, wound protection; patients with < 30% output reduction after 15 days could cross over to somatostatin	40	55.7 (35-78); mean (range)	10 (50)	Duodenum n = 5; pancreatic n = 7; jejunum n = 7; ileum n = 18; ileocolic n = 3	0	40 (100)	286.1
Scott et al[19], 19932	12	Prospective, randomized, double-blind, placebo-controlled trial	Octreotide 100 µg subcutaneously three times daily for 12 days	Placebo (acetate-buffered saline injections) for 12 days	19	61.4 (22-78)	7 (36.8)	Stomach n = 2; duodenum n = 4; pancreatic n = 2; small n = 11	NR	NR	359
Isenmann et al[20], 1994	30	Prospective, randomized, multicenter. Blinding status is unclear	IV somatostatin 250 µg/hour continuous infusion; increased to 500 µg/hour if output > 500 mL/day after 7 days; maintained until closure + 1-3 days; TPN only; NPO except 200-300 mL water/day	TPN alone; no somatostatin; NPO except 200-300 mL water/day; continued for ≥ 14 days, with possible crossover to somatostatin after 2 weeks if no improvement	45	57.7 (28-82), mean (range)	28 (68%)	Pancreatic n = 20; bile duct n = 4; small bowel n = 21	0	45 (100)	334.7
Sancho et al[21], 1995	20	Prospective, randomized, double-blind, multicenter	Early administration of octreotide (100 μg subcutaneously every 8 hours) combined with total parenteral nutrition	Placebo (1 mL 0.9% saline SC every 8 hours) + total parenteral nutrition (TPN: 40 kcal/kg/day, 0.2 g protein/kg/day, 50% glucose, 50% lipids); all received H2 blockers (cimetidine/ranitidine), nasogastric tube, and antibiotics as needed	31	64.5 (58-73); mean (range)	19 (61.29)	Stomach n = 1; duodenum n = 11; pancreatic n = 5; jejunum n = 5; ileum n = 9	NR	NR	835.7
Hernández-Aranda et al[2], 1996	28	Prospective, randomized. Blinding and center status are unclear	Octreotide 100 µg SC every 8 hours + conventional care (fluid/electrolyte replacement, skin protection, nutritional support, antibiotics); surgery if sepsis or fistula-persisting factors were present	Conventional care only: Fluid and electrolyte replacement, skin protection, nutritional support, and antibiotics; surgery if sepsis or fistula-persisting factors were present	99	50.1 (19.5); mean (SD)	55 (55.56)	Esophagus n = 11; stomach n = 10; duodenum n = 22; small bowel n = 56	84 (84.8)	15 (15.2)	NR
Leandros et al[22], 2004	NA	Prospective, randomized, single-center. Blinding status is unclear	Somatostatin group: Somatostatin 6000 IU/day IV continuous infusion + SMT. Octreotide Group: Octreotide 100 µg SC three times daily + SMT	SMT only: Fluid/electrolyte correction, nutritional support, sepsis control, and wound care	51	67 (14.7); median (SD)	31 (60.8%)	Stomach n = 4; pancreatic n = 13; bile duct n = 8; small and large bowel n = 23; other n = 3	24 (47.1)	27 (56.3)	NR
Jamil et al[23], 2004	90	Prospective, randomized, single-center. Blinding status is unclear	Octreotide 300 µg/day SC in three divided doses (100 µg TID) + standard supportive care (TPN, antibiotics, fluid/electrolyte replacement, skin/wound care, NPO until fistula output < 200 mL/day)	Standard supportive care only: TPN, antibiotics, fluid/electrolyte replacement, skin/wound care, NPO until fistula output < 200 mL/day	33	38.3 (mean)	18 (55)	Duodenum n = 2; jejunum n = 6; ileum n = 17; colon n = 4; appendicular n = 1; bibiopancreatic n = 3	NR1	NR1	NR
Gayral et al[7], 2009	NA	Prospective, randomized, double-blind, multicenter	Lanreotide 30 mg PR could receive up to 6 injections at 10-day intervals	Placebo IM injection (matching schedule) + systemic standard care (fluid/electrolyte balance, sepsis control, nutritional support)	107 (ITT n = 102)	56.9 (15); mean (SD)	59 (55.1)	Duodenum n = 18; pancreatic n = 71; small bowel n = 18	NR	NR	3369
Timmer et al[24], 2024	56	Prospective, randomized, open-label, multicenter	Standard treatment plus lanreotide 120 mg subcutaneous injection once every 4 weeks for in total 8 weeks	Standard care only: Fluid/electrolyte replacement, sepsis control, nutritional support, and wound care	17	60.6 (14); mean (SD)	10 (58.8)	Duodenum n = 2; small bowel n = 15	17 (100)	0	1484

¹Mean or median.

²High- vs low-output classification was not possible due to absence of individual-level data; only group medians were reported. Output estimates based on reported percentages; data incomplete for all 33 patients.

NR: Not reported; TPN: Total parenteral nutrition; SMT: Standard medical treatment; NPO: Nothing by mouth (nil per os); SC: Subcutaneous; TID: Three times a day; PR: Per rectum; ITT: Intent-to-treat; IM: Intramuscular.