drugset / Trial / NCT02258074
The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE
Phase 2
Completed
205 enrolled
The Cleveland Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · collab
RandomizedParallel-groupTriple-blindOther
Summary
The COMBINE clinical trial is a pilot study evaluating the effects of nicotinamide and lanthanum carbonate on serum phosphate and fibroblast growth factor 23 (FGF23) in patients with Chronic Kidney Disease (CKD) stages 3-4.
Timeline
- Start
- 2015-03
- Primary completion
- 2018-11
- Completion
- 2019-09
Outcome
Missed primary endpoint
paper Mean rates of change in phosphate increased slightly over 12 months in all groups and did not differ significantly across arms. PMID 31085679 ↗
paper Similarly, percent changes in FGF23 per 12 months increased for all arms except LC plus placebo, and did not differ significantly across arms. PMID 31085679 ↗
Publications
- Background Isakova T, Ix JH, Sprague SM, Raphael KL, Fried L, Gassman JJ, Raj D, Cheung AK, Kusek JW, Flessner MF, Wolf M, Block GA. Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD. J Am Soc Nephrol. 2015 Oct;26(10):2328-39. doi: 10.1681/ASN.2015020117. Epub 2015 May 12.
- Results Ix JH, Isakova T, Larive B, Raphael KL, Raj DS, Cheung AK, Sprague SM, Fried LF, Gassman JJ, Middleton JP, Flessner MF, Block GA, Wolf M. Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial. J Am Soc Nephrol. 2019 Jun;30(6):1096-1108. doi: 10.1681/ASN.2018101058. Epub 2019 May 13.
- Natale P, Green SC, Ruospo M, Craig JC, Vecchio M, Elder GJ, Strippoli GF. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev. 2025 Jun 27;6(6):CD006023. doi: 10.1002/14651858.CD006023.pub4.
- Trujillo J, Alotaibi M, Seif N, Cai X, Larive B, Gassman J, Raphael KL, Cheung AK, Raj DS, Fried LF, Sprague SM, Block G, Chonchol M, Middleton JP, Wolf M, Ix JH, Prasad P, Isakova T, Srivastava A. Associations of Kidney Functional Magnetic Resonance Imaging Biomarkers with Markers of Inflammation in Individuals with CKD. Kidney360. 2024 May 1;5(5):681-689. doi: 10.34067/KID.0000000000000437. Epub 2024 Apr 4.
- Srivastava A, Cai X, Lee J, Li W, Larive B, Kendrick C, Gassman JJ, Middleton JP, Carr J, Raphael KL, Cheung AK, Raj DS, Chonchol MB, Fried LF, Block GA, Sprague SM, Wolf M, Ix JH, Prasad PV, Isakova T. Kidney Functional Magnetic Resonance Imaging and Change in eGFR in Individuals with CKD. Clin J Am Soc Nephrol. 2020 Jun 8;15(6):776-783. doi: 10.2215/CJN.13201019. Epub 2020 Apr 28.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Lanthanum Carbonate | Other / unclassified | 1000 mg | Oral |
| Subject | Nicotinamide | Other / unclassified | 750 mg | Oral |