Table 3.
Overview of somatostatin trials in ADPKD and/or ADPLD patients and reporting of cyst infection and other inflammatory complications
| Author, year | Design (allocation) | Duration | Intervention | Population | Inclusion criteria | Endpoints | Hepatic cyst infection |
|---|---|---|---|---|---|---|---|
| Placebo controlled | |||||||
| Ruggenenti, 2005 [16] | Randomized, placebo-controlled, cross-over trial | 6 months | i.m. octreotide-LAR 40 mg every 28 days | 14 ADPKD (14 both intervention and placebo) | ≥18 years of age; ADPKD diagnosis; serum creatinine < 3.0 mg/dL, but > 1.2 mg/dL (men) or > 1.0 mg/dL (women) | TKV; kidney cystic volume; kidney parenchyma volume; eGFR; safety | N/A |
| Keimpema, 2009 [17] | Randomized, double-blind, placebo-controlled trial (1:1) | 24 weeks | s.c. lanreotide 120 mg every 28 days | 32 ADPKD/22 ADPLD (27 intervention, 27 placebo) | ≥18 years of age; > 20 hepatic cysts | TLV; TKV; gastrointestinal symptoms (gastrointestinal-questionnaire); HRQoL (SF-36); safety | N/A |
| Hogan, 2010 [18] | Randomized, double-blind, placebo-controlled trial (2:1) | 1 year | i.m. octreotide-LAR 40 mg every 28 days | 34 ADPKD/8 ADPLD (28 intervention, 14 placebo) | ≥18 years of age; severe hepatic cystic disease (> 4000 mL hepatic volume or symptomatic and no candidate or declining surgery) | TLV; TKV; GFR; QoL (SF-36); safety | One patient developed abdominal pain and fever |
| Caroli, 2013 [9] | Randomized, single-blind, placebo-controlled, parallel-group trial (1:1) | 3 years | i.m. octreotide-LAR 40 mg every 28 days | 79 ADPKD (40 intervention, 39 placebo) | >18 years of age; ADPKD; eGFR ≥ 40 (MDRD) | TKV; total kidney cyst volume; non-cyst kidney volume; GFR; safety | N/A |
| No placebo control group | |||||||
| Chrispijn, 2012 [19] | Open-label observational extension study of Keimpema 2009 | 6 months | s.c. lanreotide 120 mg every 28 days | 25 ADPKD/16 ADPLD (41 intervention) | ≥18 years of age; > 20 hepatic cysts; previous participation in LOCKCYST | TLV; TKV; gastrointestinal symptoms (gastrointestinal questionnaire), HRQoL (SF-36), safety | N/A |
| Hogan, 2012 [12] | Open-label extension of trial Hogan, 2010 | 1 year | i.m. octreotide-LAR 40 mg every 28 days | 32 ADPKD, 9 ADPLD (41 intervention) | ≥18 years of age; severe hepatic cystic disease (> 4000 mL hepatic volume or symptomatic and no candidate or declining surgery); previous participation in trial Hogan, 2010 | TLV; TKV; GFR; QoL (SF-36); safety | One hepatic cyst infection |
| Chrispijn, 2013 [20] | Randomized controlled, trial | 48 weeks | i.m. everolimus 2.5 mg daily + i.m. octreotide 40 mg every 28 days compared with octreotide monotherapy | 15 ADPKD, 29 ADPLD, (23 octreotide monotherapy, 21 octreotide/everolimus) | Between 18 and 70 years of age; TLV > 2500 mL hepatic; symptomatic PLD (ECOG-PS ≥ 1 and ≥ 3 PLD symptoms) | TLV; TKV; gastrointestinal symptoms (gastrointestinal questionnaire); HRQoL (EQ-5D); safety | One suspicion of cyst infection. One patient developed anemia, malaise, fever, ascites, and abdominal pain |
| Higashihara, 2015 [21] | Observational trial | 24 weeks | i.m. octreotide-LAR 40 mg every 28 days | 4 ADPKD (intervention) | Between 20 and 60 years of age; ADPKD; eGFR ≥ 45 (IDMS-MDRD); TKV ≥ 1000 mL and TLV ≥ 3000 mL | TKV; TLV; GFR; safety | N/A |
| Gevers, 2015 [13] | Observational trial | 24 weeks | s.c. lanreotide 120 mg every 28 days | 43 ADPKD (intervention) | Between 18 and 70 years of age; eGFR > 30 (MDRD); ADPKD with symptomatic (ECOG-PS ≥ 1 and ≥ 3 PLD symptoms) PLD (Gigot type II or III) | TLV; TKV; GFR; gastrointestinal symptoms (gastrointestinal questionnaire); HRQoL (EQ-5D); safety | One patient with hepatic cyst infection. Two patients with the suspicion of hepatic or renal cyst infection |
| Hogan, 2015 | Open-label observational extension study of Hogan 2012 | 2 years | i.m. octreotide-LAR 40 mg every 28 days | 28 ADPKD (intervention) |
≥18 years of age; severe hepatic cystic disease (> 4000 mL hepatic volume or symptomatic and no candidate or declining surgery); previous participation in trial Hogan, 2012 | TLV; TKV; GFR; QoL (SF-36); safety | One patient with hepatic cyst infection |
| Temmerman, 2015 | Observational trial | 6 (n = 59) or 18 months(n = 51) | s.c. lanreotide 90 mg every 28 days for 6 months, patients with reduction in TLV > 100 mL OR non-responders continued another 18 months | 51 ADPKD, 8 ADPLD (intervention) | ≥18 years of age; symptomatic PLD with hepatomegaly due to ADPKD or ADPLD | TLV; symptoms; nutritional status; TKV; GFR | N/A |
| Treille, 2014 | Case report | 6 (n = 2), 12 (n = 2) or 18 (n = 2) months | s.c. lanreotide 120 mg every 28 days | 6 ADPKD (intervention) | eGFR > 30 (MDRD) | TKV; TLV; eGFR | N/A |
ADPKD autosomal dominant polycystic kidney disease, ADPLD autosomal dominant polycystic liver disease, ECOG-PS Eastern Cooperative Oncology Group Performance Status, eGFR estimated glomerular filtration rate, EQ-5D EuroQol five dimensions questionnaire, GFR glomerular filtration rate, HRQoL health-related quality of life, IDMS-MDRD Japanese coefficient of Modified Isotope Dilution Mass Spectrometry-Modification of Diet in Renal Disease, i.m. intramuscular, LAR long-acting release, MDRD Modification of Diet in Renal Disease, N/A not available, PLD polycystic liver disease, QoL quality of life, SA somatostatin analog, s.c. subcutaneous, SF-36 Medical Outcomes Study Form 36, TKV total kidney volume, TLV total liver volume