The 3C Trial Protocol

Below we give a summary of the trial protocol. If you wish, you may download the full version of the protocol as a pdf from the following link:

3C Trial Protocol Version 5 PDF

Campath, Calcineurin inhibitor reduction and Chronic allograft nephropathy

Protocol Summary


The major challenge facing the kidney transplantation community at present is improving the long-term survival of grafts. Although there has been significant progress in reducing acute rejection in the last decade, there has been no concomitant increase in the long-term survival of kidney transplants.

Calcineurin inhibitors (CNIs, ciclosporin and tacrolimus) have improved acute rejection rates, but also contribute significantly to chronic allograft nephropathy (CAN, the commonest cause of late graft loss). Efforts have been made to reduce exposure to these agents, but these are often hampered by an increased incidence of acute and chronic rejection. Promising methods of reducing exposure to CNIs have been using ‘induction’ therapy at the time of transplantation (antibody-based treatments which dampen the immune response to the graft in the period immediately following the operation when the risk of rejection is highest) and using alternative maintenance immunosuppressants in the place of CNIs.

Campath-1H (alemtuzumab) is a humanized monoclonal antibody against CD52, which is expressed on many immune cells, and two doses around the time of surgery rapidly deplete the body of lymphocytes (the main immune cell responsible for rejection). This powerful ‘induction’ therapy allows a significant reduction in the amount of maintenance immunosuppression required, and therefore limits the exposure to CNIs. Sirolimus can be used for maintenance immunosuppression, but is not a CNI and is not nephrotoxic. Many trials have shown that switching patients from a CNI-based regimen to sirolimus has a beneficial effect on the function of the graft, which could well translate into a prolonged lifespan. Furthermore, both Campath-1H and sirolimus have potentially beneficial effects on the immune system, such that they may induce a state of near ‘tolerance’, in which the host immune system requires much less suppression to prevent it from rejecting the transplant.

The 3C study will investigate both of these approaches, and elucidate whether using Campath-1H induction with or without a switch to sirolimus-based immunosuppression improves the function, and long-term survival, of kidney transplants.


3C Study Design Diagram

Aim and Assessments

The 3C study will include 800 patients aged over 18 years old who have been listed for kidney transplantation. The primary aims are to assess the effects of allocation to:

Secondary assessments will include the effect of study treatments on

At the time of surgery, patients will be randomly allocated (using a minimization algorithm) to receive either Campath-1H or basiliximab induction. They will be allocated to their long-term maintenance therapy (sirolimus- or tacrolimus-based) by a second randomisation at six months after surgery.

Summary of Practical Procedures

Potentially eligible:

Identification and Invitation

Randomisation visit (prior to surgery)

Discharge visit, and followup visits at 1, 3, 6, and 12 months

Followup after one year, six monthly until 6 years after surgery

Monitoring of safety and efficacy

transparent area to click on