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| [ ...Back to search results ] | [ Print-friendly version ] |
| Angiotensin Converting Enzyme (ACE) inhibition for the preservation of renal function and patient survival in kidney transplantation |
| ISRCTN | ISRCTN78129473 |
| ClinicalTrials.gov identifier | |
| Public title | Angiotensin Converting Enzyme (ACE) inhibition for the preservation of renal function and patient survival in kidney transplantation |
| Scientific title | Angiotensin Converting Enzyme (ACE) inhibition for the preservation of renal function and patient survival in kidney transplantation: a randomised, double blind, placebo controlled trial |
| Acronym | N/A |
| Serial number at source | MCT-78844 |
| Study hypothesis |
The ACE-inhibitor ramipril, independent of its blood pressure lowering effect, will reduce the progression of clinically significant renal disease and mortality in renal transplant recipients with chronic kidney disease.
Please note that as of 16/07/2008 this record was updated. All changes can be found under the relevant field, with the above date of update. |
| Lay summary | |
| Ethics approval |
Approved by Ottawa Hospital Research Ethics Board, Ottawa, Ontario, Canada (21/02/2006, 15/03/2006, 05/06/2006).
Further amendments added on 16/07/2008: 14/09/2006, 24/05/2007, 25/04/2008. Further amendments added on 12/11/2009: 01/02/2008, 01/10/2009. |
| Study design | Randomised, double blind, placebo controlled trial |
| Countries of recruitment | Canada |
| Disease/condition/study domain | Chronic kidney disease in renal transplant patients |
| Participants - inclusion criteria |
Current inclusion criteria as of 16/07/2008:
Patients, either sex, who underwent the kidney transplantation and who: 1. Have an estimated glomerular filtration rate greater than or equal to 20 ml/min/1.73 m^2 using the Modification of Diet in Renal Disease study (MDRD) equation which has been validated in renal transplant patients 2. Have proteinuria = 0.2 grams/day 3. Are at least three months post-transplantation 4. Have signed informed consent Previous inclusion criteria: Patients, either sex, who underwent the kidney transplantation and who: 1. Have an estimated glomerular filtration rate between 20 and 55 ml/min using the Modification of Diet in Renal Disease study (MDRD) equation which has been validated in renal transplant patients 2. Have proteinuria = 0.2 grams/day 3. Are at least six months post-transplantation 4. Have signed informed consent |
| Participants - exclusion criteria |
1. Unable to provide informed consent
2. Less than 18 years old 3. Pregnant (ramipril contraindicated) 4. Angioedema from an ACE inhibitor or angiotensin receptor blocker or other known reaction to an ACE inhibitor (such as rash, neutropenia or cough) 5. Serum potassium greater than 5.5 mmol/l on two or more occasions in the preceding three months for those not on an ACE inhibitor or angiotensin receptor blocker 6. Serum potassium greater than 5.9 mmol/l on two or more occasions in the preceding three months for those on an ACE inhibitor or angiotensin receptor blocker 7. Left ventricular dysfunction that requires an ACE inhibitor or an angiotensin receptor blocker 8. Other severe co-morbid conditions (e.g. malignancy, disabling stroke) with life expectancy less than three months 9. New immunosuppressive agent was started or previous immunosuppressant stopped in the three months prior to study entry or plan to switch immunosuppressive agents within next three months 10. Had an acute coronary syndrome, stroke or transient ischaemic attack in the three months prior to study entry 11. Were previously enrolled in this study 12. Currently enrolled in another interventional trial 13. Currently on an ACE-inhibitor or an angiotensin receptor blocker and patient or physician unwilling to stop medication 14. Had an acute rejection episode in the three months prior to study entry 15. Currently on four or more blood pressure pills and have an average blood pressure over three visits greater than 150/100 |
| Anticipated start date | 01/07/2006 |
| Anticipated end date | 30/07/2010 |
| Status of trial | Completed |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | 528 |
| Interventions |
Experimental arm: ramipril (ALTACE®) will be given as follows: 5 mg (one capsule) daily for two weeks, then 10 mg (two capsules) daily thereafter.
Control arm: placebo capsules filled with lactose monohydrate and encapsulated into gelatin. Placebo capsules will match over-encapsulated Ramipril 5 mg (also encapsulated into gelatin with lactose monohydrate as a filler). One capsule daily for two weeks, then two capsules daily thereafter. Added as of 18/01/2010: Each participant will have an aliquot (approximately 1 cc per study visit) of serum stored for up to 15 years for: 1. Possible recalculation of creatinine 2. Quality assurance (calibration of cystatin C), and 3. Potential future testing for novel markers of kidney disease Serum samples will be stored at -80C at the EORLA Research Lab (The Ottawa Hospital General Campus). Any future testing would be submitted to a Research Ethics Board (REB) for approval. |
| Primary outcome measure(s) |
1. A composite measure incorporating the following clinically important endpoints:
1.1. Doubling of serum creatinine 1.2. End-stage renal disease or death 2. Time points of measurement: 2.1. Doubling of serum creatinine will be confirmed by two consecutive tests at least four weeks apart in a central laboratory. The base creatinine for the primary outcome will be the creatinine performed at the time of randomisation. 2.2. End-stage renal disease will be defined as the date the patient undergoes repeat kidney transplantation or starts dialysis 2.3. Death defined as the date the patient dies |
| Secondary outcome measure(s) |
1. Rate of decline in glomerular filtration rate (radioisotopic method), measured at baseline and then every six months thereafter
2. Urine protein excretion (24 hour urine), measured at baseline and then every six months thereafter 3. Systolic and diastolic blood pressure, measured at screening, baseline, one month, two months (only if BP is 130/80 mmHg at one month), six months and every six months thereafter. Amended as of 12/11/2009 to: Patients will return one month after the study visit to either their family physicians or transplant clinic for follow-up blood pressure monitoring each time their blood pressure is greater than 130/80 mmHg. 4. Incidence of adverse events: early rise in serum creatinine (greater than 30% increase from baseline), hyperkalemia (potassium = 5.5 mmol/l), and anemia (haemoglobin less than 110 g/l in women and less than 120 g/l in men), serum creatinine (Cr) and potassium will be measured at screening, baseline, two weeks, one month, six months, and every six months thereafter. At each visit, the serum Cr compared to the baseline sample taken at randomisation to determine if a doubling in Cr has occurred. Haemoglobin will be measured at baseline, two weeks, one month, six months, and every six months thereafter. 5. Incidence of cardiovascular events, documentation will be gathered for review by a blinded adjudication committee. 6. Total number of hospitalisations, will be measured at each follow-up visit (every six months) and well documented on case report forms 7. Health-related quality of life, generic (SF-36 v2 health survey) and utility measure (EuroQOL-5D). Quality of life questionnaires will be completed by patients at baseline, six months, 12 months and then annually. 8. Health care resource utilisation, will be measured at each visit - baseline and every six months thereafter Added as of 16/07/2008: 9. Clinically meaningful diagnostic characteristics of serum Cystatin C and beta trace protein will be measured at each visit-baseline and every 6 months thereafter Added as of 12/11/2009 (latest ethics amendment in October 2009): 10. Serum storage: each participant will be asked to allow any serum remaining after every 6-month testing, to be stored for up to 15 years for: 10.1. Possible recalculation of creatinine 10.2. Quality assurance (calibration of Cystatin C) 10.3. Potential future testing for novel markers of kidney disease Serum samples will be stored at -80°C at the EORLA Research Lab (The Ottawa Hospital General Campus). Any future testing would be submitted to a REB for approval. Serum will eventually be destroyed using standard operating laboratory procedures at The Ottawa Hospital. |
| Sources of funding | Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT 78844) |
| Trial website | |
| Publications |
1. 2007 protocol in http://www.ncbi.nlm.nih.gov/pubmed/17848393
2. 2008 protocol in http://www.ncbi.nlm.nih.gov/pubmed/17848393 |
| Contact name | Dr Gregory Knoll |
| Address |
The Ottawa Hospital
1967 Riverside Drive Room 515 Ottawa |
| City/town | Ontario |
| Zip/Postcode | K1H 7W9 |
| Country | Canada |
| Sponsor | Ottawa Hospital Research Institute (OHRI) (Canada) - formerly Ottawa Health Research Institute |
| Address |
501 Smyth Road
Ottawa |
| City/town | Ontario |
| Zip/Postcode | K1H 8L6 |
| Country | Canada |
| Sponsor website: | http://www.ohri.ca/home.asp |
| Date applied | 12/07/2006 |
| Last edited | 27/01/2010 |
| Date ISRCTN assigned | 13/07/2006 |
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| © 2012 ISRCTN unless otherwise stated. | |
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