Here is the design of a clinical trial:

Official Title: A Randomized Controlled Trial of Urine CXCL10 Chemokine Monitoring Post-renal Transplant

Included conditions:
- Kidney Transplant; Complications
- Rejection of Renal Transplant

Study Armgroups:
- {'label': 'Intervention', 'type': 'EXPERIMENTAL', 'description': 'Participants with high urine CXCL10 randomized to the Intervention Arm will undergo a kidney transplant biopsy to check for rejection. Biopsy-proven subclinical rejection will be treated per study protocol.', 'interventionNames': ['Procedure: Kidney transplant biopsy']}
- {'label': 'Control', 'type': 'NO_INTERVENTION', 'description': 'Participants with high urine CXCL10 randomized to the Control Arm will continue routine post-transplant surveillance with serum creatinine and proteinuria; serial urine samples will continue to be collected and analyzed (blinded), but not used to direct care.'}

Interventions:
- {'type': 'PROCEDURE', 'name': 'Kidney transplant biopsy', 'description': 'Elevated urine CXCL10 will trigger a study biopsy in patients randomized to the intervention arm. Subclinical rejection will be treated per protocol.', 'armGroupLabels': ['Intervention'], 'otherNames': ['Protocol biopsy']}

Primary Outcomes:
- {'measure': 'Death-censored graft loss', 'description': 'Return to dialysis or re-transplant', 'timeFrame': '2 weeks-12 months post-transplant'}
- {'measure': 'Clinical indication biopsy-proven acute rejection', 'description': 'Clinical rejection, Banff criteria', 'timeFrame': '2 weeks-12 months post-transplant'}
- {'measure': 'De novo donor specific antibody development', 'description': 'De novo human leukocyte antibody (HLA) antibodies, donor specific', 'timeFrame': '2 weeks-12 months post-transplant'}
- {'measure': 'Subclinical tubulitis', 'description': 'Subclinical rejection, Banff criteria', 'timeFrame': '12-month study exit biopsy'}
- {'measure': 'Interstitial fibrosis and inflammation (IFTA + i)', 'description': 'IFTA + i, defined by Mayo criteria', 'timeFrame': '12-month study exit biopsy'}

Please estimate the sample size based on the assumption: 
Alpha error 0.05, power 0.80, and 20% drop-out rate.
Sample size
        
          Sample size calculation: randomisation phase
          The TMAKP has a 2% cumulative incidence of death-censored graft loss and 13.6% clinical biopsy-proven acute rejection within the first-year post-transplant (censored for primary non-function and HLA 0âMM, 1999â2014), in a population that is not enriched for subclinical rejection by urine CXCL10. A conservative estimate of 13.6% clinical biopsy-proven acute rejection was used. The prevalence of dnDSA development varies in the literature, due to confounding by the inadequate exclusion of pretransplant DSA. In studies that exclude pretransplant DSA with a flow cross-match or solid phase assays, the prevalence of dnDSA ranges from 2.0% to 27% at 12âmonths after transplant,17 43 52â55 therefore, we assumed a conservative estimate of 2%.
          The literature demonstrates a range of IFTAÂ +Â inflammation from 9.5% to 26%, depending on the patient population, time post-transplant and biopsy indication.10 11 41â43 56 As 12-month surveillance biopsies showed a 20.2% prevalence of unfavourable prognostic features, including IFTAÂ +Â inflammation, in patients on modern immunosuppression, this was the estimate we used11 (table 1). In unselected populations, the prevalence of subclinical tubulitis at 12âmonths is 3.4%.11 However, patients with elevated urine CXCL10 have a 63% prevalence of subclinical tubulitis.28 Therefore, a conservative estimate of 17.4% subclinical tubulitis was used, as the study design enriches for patients at high risk of rejection through elevated urine CXCL10. Therefore, a conservative estimate of the overall prevalence of the primary outcome in the control arm is 55%, allowing for some overlap in endpoints.
          
            Table 1
            
              IFTAÂ + inflammation prevalence estimates
            
            
              
                
                  Study
                  Population
                  Biopsy
                  Time post-Transplant
                  Prevalence
                  Definition
                  Ref
                
              
              
                
                  Park et al

                  LD recipients 2000â2007
                  Protocol
                  1âyear
                  20/151 13%
                  Mayo
                  
41

                
                
                  Cosio et al

                  LDÂ and DD recipients 1998â2001
                  Protocol
                  1âyear
                  53/292 18%
                  Mayo
                  
10

                
                
                  Gago et al

                  LDÂ and DD recipients 2000â2006
                  Protocol: 151/207,Â 73% Indication: 56/207, 27.1%
                  16.9Â±15.5Â mos (1, 3, 5âyears)
                  207/795 26%
                  Mayo
                  
42

                
                
                  Gago et al

                  LDÂ and DD recipients 2000â2006
                  Protocol*
                  1âyear
                  14.4%
                  Mayo
                  
42

                
                
                  Cosio et al

                  LDÂ and DD recipients 1999â2010 LD=78%
                  Protocol
                  1âyear
                  86/935 9.5%â 
                  Mayo
                  
11

                
                
                  Ho et al

                  LDÂ and DD recipients
                  Protocol
                  2âyears
                  28/111 25%â¡
                  Mayo
                  
56

                
                
                  Ho et al

                  LDÂ and DD recipients
                  Protocol
                  6Â mos
                  22/94 23.4%
                  Mayo
                  
56

                
                
                  TMAKP
                  LDÂ and DD recipients
                  Protocol
                  6Â mos
                  48/222 21.6%
                  Mayo
                  
                
                
                  TMAKP
                  LDÂ and DD recipients
                  Protocol
                  6Â mo
                  Pure IFTA alone (ci+ctÂ â¥2)Â§ 93/222 41.9%
                  
                  
                
                
                  GarcÃ­a-CarroÂ etÂ al

                  LDÂ and DD recipients
                  Protocol
                  6Â wks
                  108/598 18.1%
                  Oslo
                  
43

                
                
                  GarcÃ­a-CarroÂ etÂ al

                  LDÂ and DD recipients
                  Protocol
                  1âyear
                  125/588Â¶ 21.25%
                  Oslo
                  
43

                
              
            
            
              
                The most recent Banff classification has been revised to include i-IFTAÂ as part of chronic active TCMR. Prevalence estimates for IFTAÂ +Â inflammation were used, as prior to February 2018, there was no internationally accepted definition for IFTAÂ +Â inflammation. The primary composite outcome for i-IFTA will be measured using the new Banff schema.37
              
              
                *They did not explicitly state that the 1âyear 14.4% reported IFTAÂ +Â inflammation was from protocol biopsies, but based on their treatment protocols, it is assumed to be largely protocol biopsies.
              
              
                â Reported as 9.5%, but calculated as 9.2%.
              
              
                â¡It is anticipated that later protocol biopsies would have higher rates of IFTAÂ +Â inflammation, based on 1, 3, 5-year biopsy data from Gago et al.42
              
              
                Â§Only 16 cases met the âconservative criteria for IFTAÂ +Â inflammationâ: ciÂ +ctÂ â¥2, i>0 (16/222, 7.2%). The whole table is otherwise scored with the Mayo clinic criteria for IFTAÂ +Â inflammation.
              
              
                Â¶Personal communication: Daniel SerÃ³n, Clara GarcÃ­a-Carro and Anna Reisaeter.
              
              
                DD, deceased donor; LD, living donor; mo, month; TCMR, T-cell mediated rejection; TMAKP, Transplant Manitoba Adult Kidney Program; wks, weeks.
              
            
          
          A 35.6% reduction in the primary composite outcome was considered clinically significant. The multicentre, interventional clinical transplant trials FKC008 and FKC014 had 82% and 78% of patients complete the study protocol, including 24-month protocol biopsies (Rush, personal communication). These were pharmacological interventional studies with serial surveillance biopsies and more intensive study protocols. This study protocol is much less intensive and a conservative 20% drop-out was assumed. Therefore, with an alpha error 0.05, power 0.80 and 20% drop-out rate, we will randomise 250 incident adult renal transplant patients. Sample size estimates were based on two-sample test of proportions using the power.prop.test function in R.57 There will be no interim analyses.
        
        
          Patient enrolment:Â screening phase, urine CXCL10
          We anticipate approximately 420 patients will need to be enrolled for urine CXCL10 screening to obtain 250 patients at high risk of rejection for randomisation. TMAKP had 87% patients meet the eligibility criteria of adult incident kidney transplant patients on tacrolimus and mycophenolate mofetil with HLAÂ â¥1âDR/DQ MM. We anticipate that approximately 40% patients will be persistently CXCL10 negative (low risk of rejection) on screening and will remain off-study, and 60% patients will have a confirmed elevated urine CXCL10 and undergo randomisation, based on observational studies.28